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Pharmacological approaches to nitric oxide signalling during neural development of locusts and other model insects.

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Archives of Insect Biochemistry and Physiology 64:43� (2007)
Pharmacological Approaches to Nitric Oxide Signalling
During Neural Development of Locusts and Other
Model Insects
Gerd Bicker*
A novel aspect of cellular signalling during the formation of the nervous system is the involvement of the messenger molecule
nitric oxide (NO), which has been discovered in the mammalian vascular system as mediator of smooth muscle relaxation. NO
is a membrane-permeant molecule, which activates soluble guanylyl cyclase (sGC) and leads to the formation of cyclic GMP
(cGMP) in target cells. The analysis of specific cell types in model insects such as Locusta, Schistocerca, Acheta, Manduca, and
Drosophila shows that the NO/cGMP pathway is required for the stabilization of photoreceptor growth cones at the start of
synaptic assembly in the optic lobe, for regulation of cell proliferation, and for correct outgrowth of pioneer neurons. Inhibition
of the NOS and sGC enzymes combined with rescue experiments show that NO, and potentially also another atypical messenger, carbon monoxide (CO), orchestrate cell migration of enteric neurons. Cultured insect embryos are accessible model systems
in which the molecular pathways linking cytoskeletal rearrangement to directed cell movements can be analyzed in natural
settings. Based on the results obtained from the insect models, I discuss current evidence for NO and cGMP as essential
signalling molecules for the development of vertebrate brains. Arch. Insect Biochem. Physiol. 64:43�, 2007.
� 2006
Wiley-Liss, Inc.
KEYWORDS : cGMP; cell proliferation; cell migration; growth cone; pioneer neuron; pest insects
INTRODUCTION
biochemical and immunocytochemical evidence for
NO signalling in the orthopteran nervous system,
Nitric oxide (NO) is an atypical cellular messen-
focussing mainly on the physiological roles of NO
ger that plays multiple functions in the vascular, im-
in sensory and motor circuits. In this report, I ad-
mune, and nervous system. In the vertebrate brain,
dress essential functions of this membrane-permeant
NO is a key signalling molecule that has been im-
messenger during development of the nervous sys-
plicated in cell proliferation, synaptogenesis, syn-
tem. Embryonic locusts are especially useful mod-
aptic plasticity, and neurological disease (Boehning
els of developmental neurobiology because cell
and Snyder, 2003; Godfrey and Schwarte, 2003;
biological mechanisms of axon guidance can be
Packer et al. 2003; Keynes and Garthwaite, 2004).
studied at the level of single identified neurons
For about a decade, two locust species (Locusta
(Goodman and Bate, 1981; Bentley and O扖onnor,
migratoria, Schistocerca gregaria) have been used as
1992; Boyan et al., 1995; Burrows, 1996; Legg and
key experimental animals to unravel NO-mediated
O扖onnor, 2003). In addition, this review will in-
processes in the physiology and development of
clude evidence for a functional role of NO in
hemimetabolous insects. In a former review of this
neurodevelopment from investigations of other well-
field (Bicker, 2001), I have tried to summarize the
studied holometabolous insect species.
University of Veterinary Medicine Hannover, Cell Biology, Institute of Physiology, Hannover, Germany
Contract grant sponsor: Deutsche Forschungsgemeinschaft.
*Correspondence to: Gerd Bicker, University of Veterinary Medicine Hannover, Cell Biology, Institute of Physiology, Bischofsholer Damm 15, D-30173 Hannover,
Germany. E-mail: gerd.bicker@tiho-hannover.de
Received 30 May 2006; Accepted 12 October 2006.
� 2006 Wiley-Liss, Inc.
DOI: 10.1002/arch.20161
Published online in Wiley InterScience (www.interscience.wiley.com)
44
Bicker
In nerve cells, NO is generated in an activity-
2+
stream effector proteins, including cGMP-depen-
/calmodulin-stimulated
dent protein kinases (PKG), phosphodiesterases,
nitric oxide synthases (NOS) (Bredt and Snyder
and cyclic nucleotide-gated ion channels (Lucas et
1992; Garthwaite and Boulton 1995). NOS cata-
al., 2000). It is possible to identify cellular targets
lyze the production of NO and L-citrulline from
by the capacity of NO to stimulate cGMP synthe-
L-arginine and O 2. Since this reaction requires
sis (Fig. 1). After exposure of nervous tissue to
nicotinamide adenine dinucleotide phosphate
chemicals releasing NO, the accumulation of cGMP
(NADPH) as a cofactor, NADPH-diaphorase his-
can be visualized with specific antisera to cGMP
tochemistry (NADPHd) following formaldehyde
(DeVente et al., 1987). However, it should be em-
fixation of neural tissue is a popular method for
phasized that the NOS and sGC enzyme activities
staining NOS-expressing cells (Matsumoto et al.,
may also be under the control of other regulatory
1993). In various regions of the adult locust ner-
ligands (Boehning and Snyder, 2003). Moreover,
vous system, measurements of NOS activity in cell
even though stimulation of sGC is a major trans-
homogenates of various regions correlate quite well
duction pathway of the NO signalling cascade,
with the biochemical determination of NADPHd
other transduction pathways that signal through
activity and the histochemical staining pattern of
redox events are possible (Stamler et al., 1997).
NADPHd-positive cells (M黮ler and Bicker; 1994;
Using NO-releasing compounds to induce cGMP
Elphick et al., 1995). Nevertheless, in some insects
synthesis in the locust brain, both a separate and
the results of the diaphorase staining are rather sen-
a co-localized cellular distribution of NADPHd ex-
sitive to variations in the histochemical protocol
pression and cGMP-immunoreactivity (cGMP-IR)
and some fixation conditions are even thought to
can be found (Bicker et al., 1996, 1997; Bicker and
cause
dependent process by Ca
Burrows,
Schmachtenberg, 1997; Ott et al., 2004). These
1999). Using an antiserum that recognizes a highly
anatomical studies suggest that in some regions of
conserved sequence of different mammalian NOS
the nervous system, NO may not only act as a
isoforms, it has been shown for the locust that
paracrine but also as an autocrine signal.
false-positive
results
(Ott
and
NOS-immunoreactivity (NOS-IR) does indeed co-
A further complex issue in the regulation of cel-
localize with NADPHd-positive cell bodies on
lular cGMP levels in invertebrates is the biosynthetic
double-stained cryosections of the antennal lobe
activity of other enzymes, such as the so-called
(Bicker,
ganglia
揳typical� soluble guanylyl cyclases that are mainly
(Bullerjahn and Pfl黦er, 2003). These findings
insensitive to NO and most likely function as mo-
would support the molecular identity of diapho-
lecular oxygen sensors and additional receptor
rase and NOS enzymes, at least for the central ner-
guanylyl cyclases, integral membrane proteins that
vous system.
are stimulated by peptide ligands (Morton, 2004).
2001)
and
in
the
abdominal
The product of NOS activity, NO is thought to
In contrast to the presence of several NOS genes
diffuse as a short-lived transcellular messenger from
in mammalian tissue (Bredt and Snyder 1992;
its site of production across cell membranes. Since
Garthwaite and Boulton 1995), only a single gene
NO is converted to nitrites and nitrates by react-
locus has been found in
ing with oxygen in water, it has a half life of about
Tully, 1995; Enikolopov et al., 1999). This locus
5� sec. NO acts mainly via stimulation of the
codes for an extended family of transcripts that may
heme sensor protein soluble guanylyl cyclase (sGC;
produce several NOS-related proteins (Enikopolov
Bellamy and Garthwaite, 2002). By selective bind-
et al., 1999). A genetic study suggests that NO has
ing at the heme iron of this enzyme, NO triggers a
an important function for the developing organ-
conformational shift, activating sGC to convert gua-
ism. Flies that are homozygous for a point muta-
nosine triphosphate (GTP) to cyclic guanosine
tion in the NOS gene die during late embryonic
monophosphate (cGMP), an intracellular second
and early larval stages for reasons that are not yet
messenger. cGMP can then activate various down-
known (Regulski et al., 2004). Thus, there is a need
Drosophila
Archives of Insect Biochemistry and Physiology
(Regulski and
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
45
tric oxide application by producing cGMP (Truman
et al., 1996). Sometimes cGMP-IR is not only
found in the cytosol but also in the nucleus, suggesting that cGMP may be involved in transcriptional regulation. Nuclear localization of cGMP-IR
is typical of neurons that are early in their maturational phase and is absent in cells once their synaptic contacts have been established. Some of the
NO-responsive cells are identified motoneurons
showing cGMP-IR axonal growth cones. The sensitivity to NO appears after the growth cone has
arrived at its target but before branches have started
to explore the muscle, reflecting the transition from
longitudinal elongation to the formation of lateral
Pharmacological manipulation of transcellular
branch growth. This led to the hypothesis (Ball and
NO/cGMP signal transduction. An increase in intracellu-
Truman, 1998) that cGMP plays a role in the early
lar Ca
of the donor cell stimulates the nitric oxide syn-
stages of communication between a postsynaptic
thase (NOS) enzyme. NOS activity can be blocked by bath
target and specific innervating neurons. Moreover,
application of the inhibitor 7-nitroindazole (7Ni). NO
certain sensory and interneurons also become NO
diffuses from the donor cell to a target cell, binds to the
receptive as they change from axonal outgrowth
Fig. 1
2+
heme moiety in soluble guanylyl cyclase (sGC) resulting
in the stimulation of the enzyme and consequent elevation of cGMP concentration. sGC activity is blocked by
the inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1one (ODQ) and stimulated independently from NO by
the sGC activator protoporphyrin IX free acid (Protoporphyrin IX). Synthesis of cGMP may activate protein kinase G (PKG) and regulate downstream cellular responses.
to synaptogenesis (Truman et al., 1996; Ball and
Truman, 1998). In contrast to a transient NO sensitivity during development, a set of subepidermal
plexus neurons of
Manduca
express a persistent NO-
induced cGMP-IR throughout larval life (Grueber
and Truman, 1999). NO-induced cGMP formation
has also been described in differentiating sensory
The PKG inhibitor 8-Bromo-guanosine 3�,5�-cyclic mono-
cells of the imaginal leg discs and during synaptic
phosphorothioate Rp-Isomer (RpcGMPS) blocks cellular
maturation at the larval neuromuscular junction
responses of the cGMP/PKG pathway. The NO donor so-
of
Drosophila
(Wildemann and Bicker, 1999a,b).
dium nitroprusside (SNP) and the membrane-permeable
NO and cGMP appear to regulate not only neu-
cGMP analogon 8-Bromo-cGMP (8Br-cGMP) can be ap-
romuscular connectivity but also the formation of
plied to raise cGMP levels in the target cell.
the retinal projection pattern of the visual system.
During visual system formation in
Drosophila
pu-
for complementary approaches to unravel the po-
pae, the photoreceptors respond to NO stimula-
tentially very important roles that NO may play
tion with the synthesis of cGMP during a specific
during the formation of insect nervous systems.
temporal window, while the postsynaptic optic
ganglia stain for NADPH-diaphorase (Gibbs and
NO/cGMP SIGNALING DURING FORMATION OF
Truman, 1998). Pharmacological interference with
NEURAL CONNECTIVITY
NO/cGMP signal transduction disrupts the establishment of proper retinal connections into the
One of the earliest ideas about the potential
optic lobe, such that photoreceptor axons extend
roles of NO/cGMP signaling came from expression
beyond their normal synaptic targets. There is ad-
studies of NO-induced cGMP-IR in embryonic
ditional genetic evidence for the involvement of
grasshoppers. During synaptogenesis, many iden-
sGC in retinal patterning of
tifiable nerve cell types respond to exogenous ni-
morphic mutant in the
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Drosophila
a-subunit
. A hypo-
gene of sGC
46
Bicker
shows minor defects in the retinal projection pat-
that traverse the route from their origin near the tip
tern. Pharmacological NOS inhibition on top of
of each appendage to the CNS, when distances are
the genetic defect increased visual system disorga-
short (Bate, 1976; Bentley and O扖onnor, 1992).
nization in mutants to a greater degree than in the
Pathfinding seems to involve selective adhesion of
wild type (Gibbs et al., 2001).
the growth cones to substrate bound guidance cues
In the tobacco hornworm Manduca sexta, an
and
partly
by
recognition
of
guide
post
cells
upregulation of cGMP levels parallels the phase
(Bentley and O扖onnor, 1992). In the thoracic
of synaptogenesis in the pupal antennal lobe
limb bud, two gradients of the semaphorin cell rec-
(Schachtner et al., 1998). Nearly all local interneu-
ognition molecule Sema-2a have been identified
rons
express
that are necessary for the directional guidance of
cGMP-IR in response to the steroid hormone 20-
the pioneer growth cones from the periphery to-
hydroxyecdysone. However, only in a subpopula-
wards the CNS (Isbister et al., 1999; Legg and
tion of these interneurons are cGMP elevations
O扖onnor, 2003).
of
the
developing
antennal
lobe
controlled directly by NO, possibly released by
Similar to the limb buds, the first neural path-
the many NADPHd-stained neurons of the lobe
ways in the antenna of the grasshopper are also
(Schachtner et al., 1999). Pharmacological inter-
established by two identified pairs of pioneer neu-
ference with the NO/cGMP signaling pathway re-
rons at the tip of the antennal anlage. The ventral
sults in reduction of the ubiquitous synaptic vesicle
and dorsal pioneers send their neurites in separate
protein synaptotagmin, suggesting that NO en-
pathways proximally, targeting a guide post cell at
hances the rate of synaptogenesis during develop-
the base of the antennal anlage (Bate, 1976; Ho
ment of olfactory glomeruli via cGMP (Schachtner,
and Goodman, 1982, Berlot and Goodman 1984).
2005). In summary, the appearance of a stage-de-
According to Ho and Goodman (1982) the axon
pendent NO-induced cGMP-synthesis in selective
of this base pioneer is the first peripheral process
neuronal cell types appears to be a rather com-
to reach the CNS from the antenna. It was origi-
mon developmental phenomenon both in hemi-
nally thought that the axons of the pioneers at the
and holometabolous insects, ranging from the
tip of the anlage prefigure two axonal fascicles to
primitive silverfish to highly developed lepidopter-
the brain, which are joined by later born sensory
ans and dipterans (Truman et al., 1996; Schachtner
neurons on the annular segments to form the bi-
et al., 1998; Wright et al., 1998; Wildemann and
partite antennal nerve of larval and adult stages.
Bicker, 1999a). Even though all these investigations
However, a recent re-investigation by Boyan and Wil-
have provided evidence for a role of NO/cGMP sig-
liams (2004) has suggested that the ventral and dor-
nalling during the assembly of neuronal connec-
sal tract of the antenna is not pioneered alone from
tivity, its precise cellular mechanisms are still a
the tip of the antenna, but in a stepwise manner by
mystery.
sets of pioneers arising in additional annular segments. Moreover, some of these more proximally
PIONEERING NO/cGMP SIGNALLING
located pioneers may correspond to the so-called
base pioneer mentioned in the literature to be po-
Pioneer neurons establish the first axonal path-
sitioned at various locations on the antenna (Ho
ways that are followed by later-growing axons using
and Goodman, 1982; Berlot and Goodman, 1984;
mechanisms of contact guidance. This pathfinding
Seidel and Bicker, 2000).
strategy is beautifully exemplified in grasshopper
Developmental neurobiologists are accustomed
embryos where the early axonal pathways in the
to the concept of neurite outgrowth as being
peripheral nervous system are laid down by easily
guided by the extracellular distribution of attrac-
identifiable pioneer neurons. For example, the neu-
tive and repellent guidance cues. These guidance
ral pathways in the antenna and limb are estab-
cues comprise secreted or cell surface朾ound fami-
lished by specific pairs of peripheral pioneer neurons
lies of proteins that are ligands of specific receptor
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
47
types on the membrane of motile growth cones
over, it will be interesting to know whether other
(Song and Poo, 2001; Dickson, 2002; Chilton,
neurons showing NO-induced cGMP-IR are also
2006). Within this conceptual framework, immu-
dependent on NO/cGMP for neurite outgrowth.
nocytochemical evidence for a role of the gaseous
Our recent investigations of the grasshopper em-
messenger NO in growth cone behavior of pioneer
bryo indicate that NO/cGMP is not only critical
neurons was somewhat surprising. Outgrowing
for growth cone extension of the antennal pioneers,
pioneer neurons at the tip of the antenna synthe-
but also for outgrowth of the other peripheral pio-
size cGMP in response to exogenous NO treatment
neers of the limbs (P鋞schke and Bicker, 2006).
(Seidel and Bicker, 2000). To search for potential
In molluscan neurons expressing NOS, there is
cellular sources of NO, NADPHd histochemistry
also comparable experimental evidence for an in-
was used. Parts of the epithelial cells that face the
trinsic regulation of neurite outgrowth (Van Wagenen
basal lamina in the embryonic antenna transiently
and Rehder, 1999). NO orchestrates two aspects
stain for NADPHd, suggesting transcellular NO/
of growth cone behavior in an identified neuron
Helisoma
cGMP signalling from the epithelium to the out-
from the buccal ganglion of the snail
growing pioneers. The staining of the basal parts
namely neurite outgrowth and filopodial dynam-
of epithelial cells during pioneer neuron outgrowth
ics. This neuron contains both NOS and sGC en-
is not very pronounced, but the staining intensity
zymes, which can be localized to the growth cone,
was much greater compared to the mesodermal tis-
suggesting the capability of autostimulation by
sue bordering the basal lamina. Diaphorase stain-
NO/cGMP signalling. Pharmacological manipula-
ing of the epithelial cells is visible during a period
tions in cell culture demonstrate that the effects of
ranging from about 32�% of embryonic devel-
exogenous NO application on neurite outgrowth
opment and disappears at later stages.
are mediated via cGMP, PKG, cyclic ADP ribose,
Using an embryo culture system, it can be
and intracellular Ca
2+
,
release (Van Wagenen and
shown that pharmacological inhibition of endog-
Rehder, 2001; Trimm and Rehder, 2004; Welshhans
enous NO synthase and sGC activity results in a
and Rehder, 2005).
perturbation of the pioneering pathways from the
The experimental analysis of neurite extension
tip of the antenna. To link the phenotypical defect
using individual snail and grasshopper neurons has
of disruption in pioneer outgrowth to a molecular
revealed that one of the developmental functions
inhibition of NO/cGMP formation, unspecific side
of NO/cGMP signalling serves the regulation of cel-
effects of the pharmacological enzyme inhibitors
lular motility. Thus, it is easy to imagine that en-
have to be ruled out. Since the pharmacological
dogenous NO production in developing nervous
disruption of pioneering pathways can be rescued
systems can influence the establishment of synap-
by supplementing the whole embryo culture with
tic contacts including dynamic structural changes
membrane-permeant cGMP and with a NO-inde-
during synapse maturation. Furthermore, knowl-
pendent activator of sGC (Seidel and Bicker 2000),
edge about neuronal growth regulation by NO
unspecific side effects of the enzyme blockers are
could be of practical importance in understanding
unlikely. Thus, embryonic pioneer neuron out-
general constraints of neural repair. Compared to
growth constitutes an accessible in vivo system in
wild-type, neuronal NOS knockout mice show a
which the role of NO/cGMP signaling during path-
delay in sciatic nerve regeneration and recovery of
finding can be analyzed at the level of identified
sensory-motor-function (Keilhoff et al., 2002).
nerve cells. Remodeling of the cytoskeleton pro-
These results suggest that release of NO following
vides the driving force for neurite outgrowth in any
peripheral nerve injury may play a beneficial role
developing nervous system. Therefore, it will be of
in mammalian nerve regeneration. There is mor-
importance to unravel intracellular signaling path-
phological evidence for axonal regeneration after
ways that regulate the NO/cGMP-induced changes
crushing a connective in the central nervous sys-
in the cytoskeleton of the pioneer neurons. More-
tem of the locust (P鋞schke et al., 2004). Intrigu-
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
48
Bicker
ingly, blocking the NOS pathway impairs axonal
regeneration of identified central neurons during
early development (Stern, 2006), emphasizing a
role for NO as a positive regulator of axonal regeneration mechanisms in insects.
NO WAYS FOR CELL MIGRATION IN THE
ENTERIC NERVOUS SYSTEM
Since molecular guidance cues of axonal outgrowth are also used for directed movements of
neuronal cell bodies (Song and Poo, 2001), our
laboratory (Haase and Bicker, 2003) and others
(Wright et al., 1998) were wondering if NO/cGMP
signalling might influence migration of embryonic
insect neurons. The formation of the insect stomatogastric or enteric nervous system (ENS) provides a
well-established model to study the cell biology of
neuronal migration (Hartenstein, 1997). The midgut plexus (MG) neurons of the grasshopper embryo arise in a neurogenic zone in the foregut,
forming a packet of postmitotic but immature neurons at the foregut-midgut boundary (Ganfornina
Fig. 2.
Tracings of midgut plexus development in the
et al., 1996). Subsequently, they undergo a rapid
grasshopper embryo as visualized by NO-induced cGMP-
phase of migration during which the neurons cross
immunoreactivity in somata and arborizations. Guts were
the foregut杕idgut boundary and move in four
incubated with the NO donor sodium nitroprusside (SNP)
migratory pathways on the midgut surface (Fig. 2).
and then immunostained with an anti-cGMP antiserum.
At the completion of migration, the MG neurons
Images were traced from individual preparations at the
invade the space between the four migratory path-
various developmental stages. Embryos are staged accord-
ways and extend terminal synaptic branches on the
midgut musculature.
The MG neurons of the grasshopper exhibit inducible cGMP-IR throughout the phase of migration (Fig. 3a,b) and continue to show high levels
of anti-cGMP staining in the phase of lateral neurite branching and the formation of terminal processes (Fig. 3c) (Haase and Bicker, 2003). When
ing to the percentage of embryogenesis completed (0�
100% at hatching). Each tracing shows a dorsal view of
the embryonic gut. ig, ingluvial ganglion. The midgut is
marked in gray; arrows indicate two migration pathways
that form the midgut nerves. When the midgut plexus acquires its mature configuration after 85% of development,
the cGMP-IR decreases. This view reveals two of the four
migratory pathways on top of the gut. Scale bar = 200
mm. Drawing modified from Haase and Bicker (2003).
the midgut plexus acquires its mature configuration,
the cGMP-IR decreases (Fig. 2). Thus, NO-induced
sGC activity in MG neurons is developmentally regu-
To establish a causal role of NO/cGMP signal-
lated and the timing of enzyme activity coincides
ling in the directed migration of the MG neurons,
exactly with periods of neuronal motility as well as
we used again pharmacological manipulations in
axonal outgrowth. Moreover, using NADPH-diapho-
whole embryo culture (Haase and Bicker, 2003).
rase staining as a histochemical marker for NOS,
Blocking of endogenous NO synthesis by the NOS
potential sources of NO could be identified in sub-
inhibitor 7NI (see Fig. 1) retards migration of the
sets of non-neural cells on the midgut.
MG neurons. Treatment with ODQ, a specific in-
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
Fig. 3.
49
Developmental expression of NO-induced cGMP-
velopment. The midgut neurons (mgn) are moving pos-
IR in enteric neurons. After forming a cellular packet at
teriorly in a pattern of chain migration. The leading as
the forgut-midgut boundary at 62% of embryonic devel-
well as the following neurons of one migratory pathway
opment, cGMP-IR midgut neurons began to migrate pos-
show strong cGMP-IR. C: After 80% of development, some
teriorly on the midgut. A: Lateral view of cGMP-IR enteric
midgut neurons leave the four main migratory routes to
neurons at the foregut-midgut boundary (vertical line in-
spread out between the midgut nerves. During the phase
dicates boundary) at 65% of development. At this stage,
of lateral neurite branching and the formation of terminal
cGMP-IR was present in cells of the ingluvial ganglion
processes on the midgut musculature, the midgut neu-
(ig), the enteric nerves, and neurons innervating the fo-
rons continue to exhibit strong cGMP-IR. These micro-
regut (fg). The caecae were not stained. Some of the mid-
graphs were modified from Haase and Bicker (2003). Scale
gut neurons migrated laterally to form a nerve ring near
bars = (A) 200
the foregut-midgut boundary. B: Seventy percent of de-
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
mm; (B,C) 25 mm.
50
Bicker
hibitor of sGC, also prevents the MG neuron mi-
can be used as a fluorescent probe for microscopi-
gration in a dose-dependent manner. In embryos
cal visualization of actin filaments. Palloidin stain-
treated with the specific PKG inhibitor RPcGMPS,
ing of migratory MG neurons shows F-actin bundles
MG neuron migration is significantly reduced. This
that are mainly localized in the cellular processes
effect suggests that cGMP might influence migra-
but not in the cell bodies. Conversely, under con-
tion via activating PKG.
ditions where migration is blocked by inhibitors
The disruption of MG neuron migration caused
of the NO/cGMP/PKG cascade, a dense network
by inhibiting NO production or cGMP synthesis
of F-actin bundles spans the cell body (Haase and
can be rescued by exogenous application of mem-
Bicker, 2003). In all animal cells, the important
brane-permeant cGMP and pharmacological stimu-
second messenger molecule cyclic AMP (cAMP)
lation of sGC (Fig. 1) , suggesting that in vivo a
mediates protein phosphorylation via the cyclic-
certain level of cGMP is necessary for MG neuron
AMP-dependent protein kinase A (PKA) pathway.
migration. The rescue experiments show clearly that
Activation of the cAMP/PKA cascade results in an
NO/cGMP signalling is essential for the regulation
inhibition of MG neuron migration, which is also
of neuronal migration in the developing ENS of
accompanied by a cytoskeletal rearrangement. The
the grasshopper. Since pharmacological inhibition
corresponding type of actin bundle distribution
of NOS or sGC causes no significant misrouting
would be expected in stationary cells (Brown et
of the MG neurons, there is no evidence for a di-
al., 1999). To summarize, the experimental pertur-
rectional guidance function of NO. Thus, growth
bations of the signalling cascades reveal that NO/
cone motility and guidance are separate processes.
cGMP signalling appears to act antagonistically to
Moreover, the fact that a simple, spatially homo-
cAMP/PKA signalling in the regulation of MG neu-
geneous bath application of NO donors and cGMP
ron motility and that elevated cGMP levels are es-
to the culture medium can rescue the defect in mi-
sential for the ability of migration.
gration argues against a role of NO as a guidance
factor for directed cell migration of the MG neu-
A CO-SIGNALING PATHWAY?
rons. Rather, the appearance of inducible sGC activity in the MG neurons just at the onset of
Is nitric oxide the only gaseous transmitter that
migration suggests that NO/cGMP signalling might
regulates growth cone motility? Most likely, the
be required for the initiation of migratory behav-
answer is indeed NO. Carbon monoxide (CO) is
ior. In primary cultured aortic smooth muscle cells,
produced by heme oxygenase enzymes as a by-
NO induces changes in cell shape, reorganization
product during the cleavage of heme (Boehning
of the actin cytoskeleton, and reduction of adhe-
and Snyder, 2003) and has the potential to signal
sion (Brown et al., 1999). Correspondingly, in the
among other pathways via the sGC/cGMP cascade.
grasshopper ENS, NO might be crucial as a per-
This gas is also thought to be a member of the
missive factor for the initiation and maintenance
atypical signaling molecules in the nervous system
of MG neuron migration.
(Boehning and Synyder, 2003). Immunoreactivity
Actin molecules exist either as monomers (G-
to heme oxygenase 2 (HO-2), the isoform of the
actin) or in polymerized helical filaments (F-ac-
enzyme that generates CO in neural tissue, has
tin) within the cell. Cell migration depends on
been described in the stomatogastric nervous sys-
forces generated by the polymerization of actin in
tem of crayfish (Christie et al., 2003). The pres-
cellular protrusions (Lauffenburger and Horwitz,
ence of NOS and HO-2 in distinct subsets of cells
1996). These actin-rich protrusions attach to the
suggests that both NO and CO may be messenger
substratum and contribute to the translocation of
molecules of invertebrate stomatogastric nervous
the cell. A localized enrichment of actin is also es-
systems.
sential for the motility of neuronal growth cones.
In the grasshopper embryo, the enteric neurons
The fungal toxin phalloidin binds to F-actin and
exhibit a transient immunoreactivity to the consti-
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
51
tutive isoform HO-2 while migrating on the mid-
significance of gaseous transmitters in regulating
gut (Knipp and Bicker, 2006). Pharmacological
cellular motility will clearly require more knowl-
inhibition of HO-2 enhances midgut neuron mi-
edge about how the migrating neurons integrate
gration in a gain-of-function experiment. However,
changes in cyclic nucleotide levels with the mo-
the transduction pathway of the CO signal is not
lecular guidance mechanisms for the directed
yet known. Since both messengers can bind to sGC,
movement.
but CO is less efficient than NO to stimulate cGMP
Despite the common developmental origin from
formation, a competition mechanism may regu-
a neuroepithelial placode in the foregut, the insect
late cGMP concentration and migratory behavior
enteric nervous system exhibits quite extensive varia-
of the enteric neurons.
tions in the detailed pattern of migration and design of neural connections (Hartenstein, 1997;
DIVERSITY OF ENTERIC NERVOUS SYSTEM
Ganfornina et al., 1996). For example, whereas in
DEVELOPMENT IN PEST INSECTS
Manduca specific sets of visceral muscle bands support migration of the enteric neurons on the mid-
Using cell proliferation and other molecular
gut (Copenhaver and Taghert, 1989; Copenhaver et
markers, the seminal study of Ganfornina et al.
al., 1996; Wright et al., 1998), no morphologically
(1996) has traced the ontogenesis of the stomato-
distinct muscle bands can be recognized along the
gastric ganglia, nerves, and nervous plexus on fore-
migratory pathways of the grasshopper embryo
and midgut of the grasshopper embryo. Based on
(Ganfornina et al., 1996). Instead, the migratory
this neuroanatomical framework, our lab has iden-
neurons move parallel to the longitudinal muscle
tified NO/cGMP/PKG, cAMP/PKA, and perhaps CO
bands directly on the surface of the midgut. In
signal transduction pathways as regulators of neu-
Manduca, different isoforms of the cell recognition
ronal migration on the midgut. Surprisingly, ear-
molecule fasciclin II mediate distinct aspects of the
lier investigations to prove a link between NO/
migration process, such as adhesion, fasciculation,
cGMP signalling and MG neuron migration in the
and the promotion of motility. These results can
embryo of Manduca sexta came up with a different
be
result (Wright et al., 1998). In Manduca develop-
fasciclin II molecules on the muscle bands coin-
ment, the migrating enteric neurons also show NO-
ciding with the active period of cell migration, in
sensitive sGC expression. The inhibition of NOS
vivo manipulations using blocking antibodies,
and sGC causes a reduction of terminal branch for-
antisense oligodeoxynucleotides, and other types
mation in a later phase of development both in
of perturbation techniques that interfere with the
Manduca and in the grasshopper (Wright et al.,
different isoforms (Wright and Copenhaver, 2000).
1998; Haase and Bicker, 2003) However, in con-
Similar types of perturbation experiments have not
trast to the grasshopper, inhibition of NO/cGMP
been performed in the grasshopper embryo, but it
signalling in Manduca does not affect neuronal mi-
is evident that the expression pattern of fasciclin
gration and there is no detectable NO source near
II on the midgut looks quite different during cell
the migrating enteric plexus cells (Wright et al.,
migration in the grasshopper and Manduca (Gan-
1998). These conflicting data obtained from neu-
fornina et al., 1996; Wright et al., 1998; Knipp,
ronal migration experiments might be due to spe-
unreported data).
deduced
from
the
transient
expression
of
cies-specific differences in the development of
Considering the enormous economic damage
holometabolous versus hemimetabolous insects.
that locust plagues can do to pastures and crops,
Differences in the experimental procedures of ani-
we actually know very little about the cellular dif-
mal culture or the effective concentration of the
ferentiation of the enteric nervous system which
pharmacological agents may have also contributed
contains the pattern generating networks (Ayali,
to the different outcome of the cell migration ex-
2004) that drive the locust抯 feeding machinery. The
periments. A full understanding of the biological
molecular identification of the guidance factors in
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
52
Bicker
economically important insect species may help to
sGC blocker does not affect antennal lobe mor-
unravel the detailed cellular mechanisms of sto-
phology. Based on evidence from an enzyme in-
matogastric nervous system formation. Perhaps,
hibitor, Gibson et al. (2001) suggest that the NO
these guidance cues might also provide us with
effect may be mediated at least in part by ADP-
novel molecular targets selective for pest insects.
ribosylation of target cell proteins.
To this end, comparative investigations of pest
and beneficial insects are required. Clearly, ubiq-
NO COORDINATES NEUROGENESIS
uitous cellular signalling cascades, such as cAMP/
PKA or NO/cGMP/PKG, which are common to
Both in vertebrates and invertebrates, NO is not
many organisms, are useless as specific targets for
only implicated in the formation of neural connec-
insecticides. Therefore, our lab has also started to
tivity but also in the proliferation of neuronal pre-
investigate the expression of specific neuroactive
cursors (Enikolopov et al., 1999; Packer et al., 2003;
compounds and of cell surface molecules during
Moreno-Lopez et al., 2004). In
the formation of the stomatogastric nervous sys-
tion of NOS results in excessive growth of body
tem (Bicker et al., 2004; Stern et al., 2006; Knipp,
structures whereas the ectopic expression of a NOS
unreported data).
transgene has the opposite effect (Kuzin et al.,
Drosophila
, inhibi-
1996). Thus, NO signalling regulates morphogenesis by controlling the balance between cell prolif-
A ROLE FOR NO IN GLIAL MIGRATION
eration and cell differentiation. The antiproliferative
During the development of the antennal lobe
Manduca
action of NO appears not to be mediated by cGMP.
, the afferent
Using an inducible transgene of NOS, overex-
olfactory receptor neurons initially arborize in
pression of genes encoding cell cycle regulatory
nodular neuropile structures that are called proto-
pathways, and pharmacological manipulations, the
glomeruli (Tolbert et al., 2003). A specific type of
mechanisms of the antiproliferative activity of NO
glial cell is then required to migrate to surround
have been analyzed during the formation of the
these protoglomeruli and to delineate the borders
compound eye (Kuzin et al., 2000). The
in the olfactory system of
Drosophila
of the developing glomeruli. If the olfactory axons
combined data argue for a role of NO in regulat-
are prevented to enter the antennal lobe, glial cells
ing cell divisions of the developing eye disc via
do not migrate and the arborisations of sensory
interaction with components of the retinoblastoma
and central neurons fail to develop into the char-
pathway. The notion that NO is involved in cell
acteristic glomerular architecture (Tolbert et al.,
cycle regulation has been reinforced by studying
2003). Thus glial cell migration plays a prominent
the development of the optic anlage in
role in the formation of the olfactory neuropile.
(Champlin and Truman, 2000). Here, proliferation
Because the olfactory receptor axons express
of neural precursors in the optic lobe of
Manduca
Manduca
NOS throughout development (Gibson and Nig-
is controlled by ecdysteroid levels and by local pro-
horn, 2000), NO release may trigger glial cell mi-
duction of NO. NADPHd staining, NOS immuno-
gration. The treatment with a NOS blocker and NO
cytochemistry, and a fluorescent NO-indicator
scavengers disrupts the glial migration to form nor-
show that cells throughout the optic anlage can
mal glomerular borders, resulting in a misshapen
synthesize NO. Opposing ecdysteroid stimulatory
glomerular neuropile (Gibson et al., 2001). This
pathways and the antiproliferatory NO pathway
result suggests that NO released from the olfac-
lead to a sharpening of the responsiveness to the
tory receptor axons is a signal to induce the glial
steroid, thereby facilitating a tight coordination
migration. Interestingly, the effects of NO release
between development of the different elements of
do not appear to be mediated by sGC, as the glial
the adult visual system.
cGMP-IR
During early larval stages, neuroblasts in the
(Gibson and Nighorn, 2000) and application of a
optic anlage undergo symmetric divisions to in-
cells
display
no
visible
NO-induced
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
crease the number of precursor cells. NOS appears
FROM DEVELOPMENTAL TIMING TO
in the optic anlage when the neuroblasts shift to
ADULT SYNAPTIC PLASTICITY
53
the asymmetric mode of division (Champlin and
Truman, 2000). This developmental phenomenon
Similar to the many physiological roles of NO
may be specific for neurogenesis in the brain, since
in the adult organism, the multitude of NO sig-
we never could resolve distinct NADPHd staining
nalling functions in development is only gradu-
in the asymmetrically dividing neuroblasts of the
ally becoming recognized (Enikolopov et al., 1999;
grasshopper and Drosophila ventral nerve cord (e.g.,
Moroz, 2001; Yamamoto et al., 2003; Krumenacker
Wildemann and Bicker, 1999a), whereas prolifera-
and Murad, 2006). The complex task of wiring
tive cell clusters of the embryonic grasshopper
brains is essentially based on the specific expres-
protocerebrum show NADPH-diaphorase expres-
sion and recognition of extracellular guidance cues.
sion (Seidel and Bicker, 2002).
The outgrowing neurites do, however, also require
In certain insect species, such as crickets and
detailed timing information concerning when to
some beetles, new neurons are also born in the
advance, when to stop, and when to wait. Thus, it
adult animal. In the house cricket Acheta domesticus,
is not unlikely to imagine that focal release of NO
adult neurogenesis occurs in the mushroom bod-
may coordinate the behavior of motile growth
ies (Cayre et al., 1994). These neuroanatomical
cones. Since production of NO is a tightly regu-
structures of the insect brain are composed of the
lated process (Bredt and Snyder 1992; Garthwaite
parallel projecting Kenyon cells that receive multi-
and Boulton 1995), increases in cytosolic Ca
modal sensory input mainly from the antennal
els (M黮ler and Bicker, 1994) could provide a de-
lobes and also from other regions of the nervous
velopmental timing signal for the production of
system
(Strausfeld
et
al.,
1998;
Bicker,
2+
lev-
1999;
NO. The timed generation of NO signals might
Fahrbach, 2006). The mushroom bodies have been
then affect cytoskeletal rearrangement to initiate
implicated in olfactory memory formation, con-
and maintain neurite growth. Whether localized
text generalization in visual learning, and complex
release of NO causes growth cone steering in vivo
integrative functions (Heisenberg, 2003; Fahrbach,
remains an open question.
2006). Neurogenesis in the cricket can be modu-
In the developing vertebrate nervous system, evi-
lated through juvenile hormone, sensory input, and
dence for the involvement of NO signalling in cell
NO signaling. Electrical stimulation of the anten-
motility can be deduced from the transient expres-
nal nerve mimicking odor sensation increases
sion of NOS in migrating neurons (Santacana et al.,
mushroom body neurogenesis (Cayre et al., 2005).
1998; Ding et al. 2005) or from the expression of
In vivo and in vitro experiments show that NOS
sGC in migrating cells (Currie et al., 2006) includ-
inhibition decreases, and NO donor application
ing neuroblasts of the rostral migratory stream
stimulates neuroblast proliferation. NADPH-d
(Martinez-Guijarro et al., 2006). However, studies
staining, anti-L-citrulline immunocytochemistry,
using experimental perturbations of NO/cGMP sig-
and in situ hybridization with a probe specific for
naling remain rather scarce (but see Tanaka et al.,
Acheta NOS provide evidence that intrinsic mush-
1994). Intriguingly, in vitro investigations using cor-
room body neurons synthesize NO. Rearing crick-
tical brain slices (Polleux et al., 2000) have shown
ets in an enriched sensory environment induces
that an asymmetric expression of sGC controls the
an upregulation of Acheta NOS mRNA, and uni-
orientation of apical dendrites in cortical pyrami-
lateral electrical stimulation of the antennal nerve
dal neurons. Mutant mice deficient in an isoform of
results in increased L-citrulline immunoreactivity
PKG display defects in neocortical development that
in the corresponding mushroom body (Cayre et
can be ascribed to abnormal neuronal migration or
al., 2005). Thus, neural activity modulates progeni-
positioning (Demyanenko et al., 2005). All of these
tor cell proliferation via a stimulatory effect of NO
results argue for an important role of cGMP/PKG sig-
on mushroom body neuroblast proliferation.
nalling in the development of the cerebral cortex.
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
54
Bicker
Our embryo culture experiments show that the
Bellamy TC, Garthwaite J. 2002. Pharmacology of the nitric
regulation of neuronal cell migration by NO/cGMP
oxide receptor, soluble guanylyl cyclase, in cerebellar cells.
involves NO-induced alterations in the actin cy-
Br J Pharmacol 136:95�3.
toskeleton (Haase and Bicker, 2003). A reorganisation of the actin cytoskeleton does not only
regulate cell motility during development. During
Bentley D, O扖onnor TP. 1992. Guidance and steering of peripheral pioneer growth cones in grasshopper embryos.
In: Letourneau C, Kater SB, Macagno, ER, editors. The
adult synaptic plasticity, activity-dependent spine
nerve growth cone. New York: Raven Press Ltd. p 265�
remodeling is also driven by changes in the dy-
282.
namic equilibrium between F-actin and G-actin.
For example, tetanic stimulation causes a rapid shift
of the actin equilibrium toward F-actin in the den-
Berlot K, Goodman CS. 1984. Guidance of peripheral pioneer neurons in the grasshopper: adhesive hierarchy of
epithelial and neuronal surfaces. Science 223:493�6.
dritic spines of rat hippocampal neurons (Okamoto
et al., 2004). Release of NO has been implicated as
Bicker G. 1999. Histochemistry of classical neurotransmit-
retrograde messengers associated with long-term
ters in antennal lobes and mushroom bodies of the hon-
potentiation in the hippocampus (Hawkins et al.,
eybee. Microsc Res Tech 45:174�3.
1998). The NO/sGC/PKG signalling cascade and
proteins that regulate the actin cytoskeleton contribute to the aggregation of synaptic proteins as a
Bicker G. 2001. Nitric oxide: an unconventional messenger
in the nervous system of an orthopteroid insect. Arch Insect Biochem Physiol 48:100�0.
form of structural plasticity in long-lasting potentiation (Wang et al., 2005). Thus, NO may affect
neurotransmission by acting on components of the
synaptic cytoskeleton. Since insects also display
Bicker G, Schmachtenberg O. 1997. Cytochemical evidence
for nitric oxide/cyclic GMP signal transmission in the visual system of the locust. Eur J Neurosci 9:189�3.
striking examples of structural plasticity during the
Bicker G, Schmachtenberg O, De Vente J. 1996. The nitric
development and functioning of their nervous sys-
oxide/cyclic GMP messenger system in olfactory pathways
tems (e.g., Fahrbach, 2006), it may be useful to
of the locust brain. Eur J Neurosci 8:2635�43.
search for contributions of NO signalling to the
underlying changes in the neuronal cytoskeleton.
Bicker G, Schmachtenberg O, De Vente J. 1997. Geometric
considerations of nitric oxide-cyclic GMP signalling in the
glomerular neuropil of the locust antennal lobe. Proc R
ACKNOWLEDGMENTS
This review is based on a symposium talk at the
XXII International Congress of Entomology, Brisbane, Australia. I thank David Stanley and Jozef
Vanden Broeck for organizing the symposium. Arne
P鋞schke helped with the preparation of the figures.
LITERATURE CITED
Soc Lond B 264:1177�81.
Bicker G, Naujock M, Haase A. 2004. Cellular expression patterns of acetylcholinesterase activity during grasshopper
development. Cell Tissue Res 317:207� 220.
Boehning D, Snyder SH. 2003. Novel neural modulators.
Annu Rev Neurosci 26:105�1.
Boyan GS, Williams JLD. 2004. Embryonic development of
the sensory innervation of the antenna of the grasshop-
Ayali A. 2004. The insect frontal ganglion and stomatogas-
per Schistocerca gregaria. Arthropod Struct Dev 33:381�7.
tric pattern generator networks. Neurosignals 13:20�.
Boyan
G,
Therianos
S,
Williams
JL,
Reichert
H.
1995.
Ball EE, Truman JW. 1998. Developing grasshopper neurons
Axogenesis in the embryonic brain of the grasshopper
show variable levels of guanylyl cyclase activity on arrival
Schistocerca gregaria: an identified cell analysis of early
of their targets. J Comp Neurol 394:1�.
brain development. Development 121:75�.
Bate CM. 1976. Pioneer neurones in an insect embryo. Nature 260:54�.
Bredt DS, Snyder SH. 1992. Nitric oxide, a novel neuronal
messenger. Neuron 8:3�.
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
Brown C, Pan X, Hassid A. 1999. Nitric oxide and C-type
atrial natriuretic peptide stimulate primary aortic smooth
55
velopment in mice lacking cGMP-dependent protein kinase I. Brain Res Dev Brain Res 160:1�
muscle cell migration via a cGMP-dependent mechanism:
relationship to microfilament dissociation and altered cell
De Vente J, Steinbusch HWM, Schipper J. 1987. A new approach to immunocytochemistry of 3�,5�-cyclic guanosine
morphology. Circ Res 84:655�7.
monophosphate: preparation, specificity, and initial apBullerjahn A, Pfl黦er HJ. 2003. The distribution of putative
plication of a new antiserum against formaldehyde-fixed
nitric oxide releasing neurones in the locust abdominal
3 � ,5 � -cyclic
nervous system: a comparison of NADPHd histochemis-
22:361�3.
guanosine
monophosphate.
Neuroscience
try and NOS-immunocytochemistry. Zoology 106:3�.
Dickson B J. 2002. Molecular mechanisms of axon guidance.
Burrows M. 1996. The neurobiology of an insect brain. New
Science 298:959�4.
York: Oxford University Press.
Ding JD, Burette A, Weinberg RJ. 2005. Expression of soluble
Cayre M, Strambi C, Strambi A. 1994. Neurogenesis in adult
insect brain and its hormonal control. Nature 368:57�
Cayre M, Malaterre J, Scotto-Lomassese S, Holstein GR,
Martinelli GP, ForniC, Nicolas S, Aouane A, Strambi C,
Strambi A. 2005. A role for nitric oxide in sensory-induced
guanylyl cyclase in rat cerebral cortex during postnatal development. J Comp Neurol 485:255�5.
Elphick MR, Rayne RC, Riveros-Moreno V, Moncada S, O扴hea
M. 1995. Nitric oxide synthesis in locust olfactory interneurones. J Exp Biol 198:821�9.
neurogenesis in an adult insect brain. Eur J Neurosci
21:2893�02.
Enikolopov G, Banerji J, Kuzin B. 1999. Nitric oxide and
Drosophila development. Cell Death Differ 6:956�3.
Champlin DT, Truman JW. 2000. Ecdysteroid coordinates optic lobe neurogenesis via a nitric oxide signaling pathway.
Development 127:3543�51.
Fahrbach SE. 2006. Structure of the mushroom bodies of the
insect brain. Annu Rev Entomol 51:209�2.
Chilton JK. 2006. Molecular mechanisms of axon guidance.
Dev Biol 292:13�.
Ganfornina MD, Sanchez D, Bastiani MJ. 1996. Embryonic
development of the enteric nervous system of the grass-
Christie AE, Edwards JM, Cherny E, Clason TA, Graubard K.
2003. Immunocytochemical evidence for nitric oxide- and
carbon monoxide-producingneurons in the stomatogastric nervous system of the crayfish Cherax quadricarinatus.
hopper Schistocerca americana. J Comp Neurol 372:581�
596.
Garthwaite J, Boulton CL. 1995. Nitric oxide signalling in
the central nervous system. Annu Rev Physiol 57:683�6.
J Comp Neurol 467:293�6.
Copenhaver PF, Taghert PH. 1989. Development of the enteric nervous system in the moth. I. Diversity of celltypes
and the embryonic expression of FMRFamide-related neuropeptides. Dev Biol 131:70�.
Gibbs SM, Truman WT. 1998. Nitric oxide and cyclic GMP
regulate retinal patterning in the optic lobe of Drosophila.
Neuron 20:83�.
Gibbs SM, Becker A, Hardy RW, Truman JW. 2001. Soluble
Copenhaver PF, Horgan AM, Combes S. 1996. An identified
set of visceral muscle bands is essential for the guidance
of migratory neurons in the enteric nervous system of
guanylate cyclase is required during development for visual system function in Drosophila. J Neurosci 21:7705�
7714.
Manduca sexta. Dev Biol 179:412�6.
Gibson NJ, Nighorn A. 2000. Expression of nitric oxide synCurrie DA, de Vente J, Moody WJ. 2006. Developmental ap-
thase and soluble guanylyl cyclase in the developing olfac-
pearance of cyclic guanosine monophosphate (cGMP) pro-
tory system of Manduca sexta. J Comp Neurol 422:191�5.
duction and nitric oxide responsiveness in embryonic
mouse cortex and striatum. Dev Dyn 235:1668�77.
Gibson NJ, R鰏sler W, Nighorn AJ, Oland LA, Hildebrand
JG, Tolbert LP. 2001. Neuron-glia communication via ni-
Demyanenko GP, Halberstadt AI, Pryzwansky KB, Werner C,
Hofmann F, Maness PF. 2005. Abnormal neocortical de-
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
tric oxide is essential in establishing antennal-lobe structure in Manduca sexta. Dev Biol 240:326�9.
56
Bicker
Godfrey EW, Schwarte RC. 2003. The role of nitric oxide sig-
Kuzin B, Regulski M, Stasiv Y, Scheinker V, Tully T, Enikolopov
naling in the formation of the neuromuscularjunction. J
G. 2000. Nitric oxide interacts with the retinoblastoma
Neurocytol 32:591�2.
pathway to control eyedevelopment in Drosophila. Curr
Biol 10:459-462.
Goodman CS, Bate CM. 1981. Neuronal development in the
grasshopper. Trends Neurosci 4:163�9.
Lauffenburger DA, Horwitz AF. 1996. Cell migration: a physically integrated molecular process. Cell 84:359�9.
Grueber WB, Truman JW. 1999. Development and organization of a nitric-oxide-sensitive peripheral neuralplexus in
larvae
of
the
moth,
Manduca
sexta . J Comp Neurol
404:127�1.
Legg AT, O扖onnor TP. 2003. Gradients and growth cone guidance of grasshopper neurons. J Histochem Cytochem
51:445�4.
Haase A, Bicker G. 2003. Nitric oxide and cyclic nucleotides
Lucas KA, Pitari GM, Kazerounian S, Ruiz-Stewart I, Park J,
are regulators of neuronal migration in an insect embryo.
Schulz S,Chepenik KP, Waldman SA. 2000. Guanylyl cy-
Development 130:3977�87.
clases and signaling by cyclic GMP. Pharmacol Rev 52:375�
414.
Hartenstein V. 1997. Development of the insect stomatogastric nervous system. Trends Neurosci 20:421�7.
Martinez-Guijarro FJ, Gutierrez-Mecinas M, Gracia-Llanes FJ,
Marques-Mari AI, Varea E, Nachev J, Blasco-Ib狁ez JM,
Hawkins RD, Son H, Arancio O. 1998. Nitric oxide as a retrograde messenger during long-term potentiation in hippocampus. Prog Brain Res 118:155�2.
Heisenberg M. 2003. Mushroom body memoir: from maps
to models. Nat Rev Neurosci 4:266�5.
Ho RK, Goodman CS. 1982. Peripheral pathways are pioneered by an array of central and peripheral neurones in
grasshopper embryos. Nature 297:404�6.
Crespo C. 2006. Migrating neuroblasts of the rostral migratory stream are putative targets for the action of nitric
oxide. FENS Forum Abstracts A122.16.
Matsumoto T, Nakane M, Pollock JS, Kuk JE, F鰎stermann U.
1993. A correlation between soluble brain nitric oxide synthase and NADPH-diaphorase activity is only seen after
exposure of the tissue to fixative. Neurosci Lett 155:61�
64.
Isbister CM, Tsai A, Wong ST, Kolodkin AL, O扖onnor TP.
Moreno-Lopez B, Romero-Grimaldi C, Noval JA, Murillo-
1999. Discrete roles for secreted and transmembrane
Carretero M, Matarredona ER, Estrada C. 2004. Nitric ox-
semaphorins in neuronal growth cone guidance in vivo.
ide is a physiological inhibitor of neurogenesis in the adult
Development 126:2007�19.
mouse subventricular zone and olfactory bulb. J Neurosci
24:85�.
Keilhoff G, Fansa H, Wolf G. 2002. Differences in peripheral
nerve degeneration/regeneration between wild-type and
neuronal nitric oxide synthase knockout mice. J Neurosci
Moroz LL. 2001. Gaseous transmission across time and species. Amer Zool 41:304�0.
Res 68:432�1.
Morton DB. 2004. Atypical soluble guanylyl cyclases in DrosoKeynes RG, Garthwaite J. 2004. Nitric oxide and its role in
ischaemic brain injury. Curr Mol Med 4:179�1.
Knipp S, Bicker G. 2006. The gaseous messenger molecules
CO and NO regulate neuronal cell migration in an insect
phila can function as molecular oxygen sensors. J Biol
Chem 279:50651�653.
M黮ler U, Bicker G. 1994. Calcium activated release of nitric
oxide and cellular distribution of nitric oxide synthesiz-
embryo. FENS Forum Abstracts A122.14.
ing neurons in the nervous system of the locust. J Neurosci
Krumenacker JS, Murad F. 2006. NO-cGMP signaling in de-
14:7521�28.
velopment and stem cells. Mol Genet Metab 87:311�4.
Okamoto K, Nagai T, Miyawaki A, Hayashi Y. 2004. Rapid
Kuzin B, Roberts I, Peunova N, Enikolopov G. 1996. Nitric
and persistent modulation of actin dynamics regulates
oxide regulates cell proliferation during Drosophila devel-
postsynapticreorganization underlying bidirectional plas-
opment. Cell 87:639�9.
ticity. Nat Neurosci 7:1104�12.
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
Nitric Oxide Signaling During Insect Development
57
Ott SR, Burrows M. 1999. NADPH diaphorase histochemis-
Schachtner J, Homberg U, Truman JW. 1999. Regulation of
try in the thoracic ganglia of locusts, crickets, and cock-
cyclic GMP elevation in the developing lobe of the sphinx
roaches: species differences and the impact of fixation. J
moth, Manduca sexta. J Neurobiol 41:359�5.
Comp Neurol 410:387�7.
Seidel C, Bicker G. 2000. Nitric oxide and cyclic GMP influOtt SR, Delago A, Elphick MR. 2004. An evolutionarily conserved mechanism for sensitization of soluble guanylyl-
ence axonogenesis of antennal pioneer neurons. Development 127:4541�49.
cyclase reveals extensive nitric oxide-mediated upregulation
of cyclic GMP in insect brain. Eur J Neurosci 20:1231�
Seidel C, Bicker G. 2002. Developmental expression of nitric
oxide/cyclic GMP signaling pathways in the brain of the em-
1244.
bryonic grasshopper. Brain Res Dev Brain Res 138:71�.
Packer MA, Stasiv Y, Benraiss A, Chmielnicki E, Grinberg A,
Westphal H, Goldman SA, Enikolopov G. 2003. Nitric oxide negatively regulates mammalian adult neurogenesis.
Proc Natl Acad Sci USA 100:9566�71.
Song H, Poo MM. 2001. The cell biology of neuronal navigation. Nat Cell Biol 3:81�.
Stamler JS, Toone EJ, Lipton SA, Sucher NJ. 1997. (S)NO Sig-
P鋞schke A, Bicker G. 2006. Influence of NO/cGMP on the
growth of peripheral pioneer neurons in the grasshopper.
Berlin, Germany: Neuro-DoWo Abstracts.
nals: translocation, regulation, and a consensus motif.
Neuron 18:691�6.
Stern M. 2006. Nitric oxide regulates neuronal regeneration
P鋞schke A, Bicker G, Stern M. 2004. Axonal regeneration of
proctolinergic neurons in the central nervous system of
the locust. Brain Res Dev Brain Res 150:73�.
in the locust embryo. Abstract 99
th
DZG Meeting, M黱ster,
Germany.
Stern M, Knipp S, Bicker G. 2006. Embryonic differentiation
of serotonin-containing neurons in the enteric nervous sys-
Polleux F, Morrow T, Ghosh A. 2000. Semaphorin 3A is a
chemoattractant
for
cortical
apical
dendrites.
Nature
tem of the locust (Locusta migratoria) J Comp Neurol (in
press)
404:557�3.
Strausfeld NJ, Hansen L, Li Y, Gomez RS, Ito K. 1998. EvoluRegulski M, Tully T. 1995. Molecular and biochemical characterization of dNOS: a Drosophila Ca
2+
/calmodulin de-
tion, discovery, and interpretations of arthropod mushroom bodies. Learn Mem 5:11�.
pendent nitric oxide synthase. Proc Natl Acad Sci USA
92:9072�76.
Tanaka M, Yoshida S, Yano M, Hanaoka F. 1994. Roles of
endogenous nitric oxide in cerebellar cortical evelopment
Regulski M, Stasiv Y, Tully T, Enikolopov G. 2004. Essential
in slice cultures. Neuroreport 5:2049�52.
function of nitric oxide synthase in Drosophila. Curr Biol.
14:881�2.
Tolbert LP, Oland LA, Christensen TC, Goriely AR. 2003. Neuronal and glial morphology in olfactory systems: significance
Santacana M, Uttenthal LO, Bentura ML, Fernandez AP,
Serrano J, Martinez deVelasco J, Alonso D, Martinez-
for information-processing and underlying developmental
mechanisms. Brain Mind 4:27�.
Murillo R, Rodrigo J. 1998. Expression of neuronal nitric
oxide synthase during embryonic development of the rat
cerebral cortex. Brain Res Dev Brain Res 111:205�2.
Trimm KR, Rehder V. 2004. Nitric oxide acts as a slow-down
and search signal in developing neurites. Eur J Neurosci
19:809�8.
Schachtner J. 2005. Regulation and role of the NO/cGMP signaling pathway during antennal lobe development of the
sphinx moth Manduca sexta. Proc 6
th
German Neurosci
Soc Conf Stuttgart. New York: Thieme Verlag. 1999 p.
Truman JW, De Vente J, Ball EE. 1996. Nitric oxide-sensitive
guanylate cyclase activity is associated with the maturational phase of neuronal development of insects. Development 122:3949�58.
Schachtner J, Klaassen L, Truman JW. 1998. Metamorphic control of cyclic guanosine monophosphate expression in the
Van Wagenen S, Rehder V. 1999. Regulation of neuronal
nervous system of the tobacco hornworm, Manduca sexta.
growth cone filopodia by nitric oxide. J Neurobiol 39:168�
J Comp Neurol 396:238�2.
185.
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
58
Bicker
Van Wagenen S, Rehder V. 2001. Regulation of neuronal
growth cone filopodia by nitric oxide depends on soluble
guanylyl cyclase. J Neurobiol 46:206�9.
Wildemann B, Bicker G. 1999b. Nitric oxide and cyclic GMP
induce vesicle release at Drosophila neuromuscular junction. J Neurobiol 39:337�6.
Wang HG, Lu FM, Jin I, Udo H, Kandel ER, de Vente J, Walter
U, Lohmann SM,Hawkins RD, Antonova I. 2005. Presynaptic and postsynaptic roles of NO, cGK, and RhoA in
long-lasting potentiation and aggregation of synaptic pro-
Wright JW, Copenhaver PF. 2000. Different isoforms of
fasciclin II play distinct roles in the guidance of neuronal
migration during insect embryogenesis. Dev Biol 225:59�
78.
teins. Neuron 45:389�3.
Wright JW, Schwinof KM, Snyder MA, Copenhaver F. 1998. A
Welshhans K, Rehder V. 2005. Local activation of the nitric
delayed role for nitric oxide-sensitive guanylate cyclases
oxide/cyclic guanosine monophosphate pathway in growth
in a migratory population of embryonic neurons. Dev Biol
cones regulates filopodial length via protein kinase G, cy-
204:15�.
clic
ADP
ribose
and
intracellular
Ca
2+
release.
Eur
J
Neurosci 22:3006�16.
Yamamoto T, Yao Y, Harumi T, Suzuki N. 2003. Localization
of the nitric oxide/cGMP signaling pathway-related genes
Wildemann B, Bicker G. 1999a. Developmental expression of
and influences of morpholino knock-down of soluble
nitric oxide / cyclic GMP synthesizing cells in the nervous
guanylyl cyclase on medaka fish embryogenesis. Zool Sci
system of Drosophila melanogaster. J Neurobiol 38:1�.
20:181�1.
Archives of Insect Biochemistry and Physiology
January 2007
doi: 10.1002/arch.
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