Septation of the respiratory and digestive tracts in human embryosCrucial role of the tracheoesophageal sulcus.

THE ANATOMICAL RECORD 238:237-247 (1994)
Septation of the Respiratory and Digestive Tracts in Human
Embryos: Crucial Role of the Tracheoesophageal Sulcus
KATHARINE S. SUTLIFF AND GROVER M. HUTCHINS
Departments of Art as Applied to Medicine and Pathology, The Johns Hopkins Medical
Institutions, Baltimore, Maryland
ABSTRACT
Esophageal atresia and tracheoesophageal fistula, common malformations of the respiratory and digestive tracts, are of unsettled
pathogenesis. Part of the difficulty in understanding these abnormalities
arises from the uncertainties about the normal developmental processes in
the region. This study examined the development and fate of the tracheoesophageal septum. Normal human embryos from the Carnegie Embryological Collection and fetuses from the Hopkins Pathology Collection were
examined, and reconstructions of selected specimens were made from photomicrographs of serial histologic sections. The results show that the lung
bud appears in Carnegie stage 12, rapidly enlarges, and bends caudally,
thereby producing a sulcus between the foregut and the respiratory system
on its caudal aspect. The cranial aspect of this tracheoesophageal sulcus
remains fixed at the levels of the first cervical vertebra throughout subsequent embryonic and fetal development. At the same time the trachea and
esophagus elongate to bring those parts of the respiratory and digestive
systems into their definitive anatomic positions. Examination of the tracheoesophageal sulcus shows that its growth-limiting properties may be
explained by its catenoidal configuration. Catenoidal, or saddle-shape,
sulci have been shown to have similar regional growth-limiting properties
in the embryonic heart. These regions contrast with outwardly convex regions in both the developing heart and lung where growth of the tissues
occurs. The observations made here suggest that the origin of the tracheoesophageal malformations must be sought in a configurational abnormality in the area of the developing lung bud in Carnegie stage 12.
0 1994 Wiley-Liss, Inc.
Key words: Embryonic development, Esophagus, Growth, Trachea
During Carnegie stage 12 and 13 in the development
of the human embryo, the respiratory system appears as
a ventral outgrowth of the foregut, generally referred to
as the lung bud, and acquires its relationship to the
foregut and other mediastinal structures. The mesenchyme that separates the respiratory and digestive
tubes is known as the tracheoesophageal septum. The
development of the human respiratory and digestive
tracts has been described. The classical account of the
development of the human trachea and esophagus appears in The Manual ofHuman Embryology (Keibel and
Mall, 1912).A later publication by Smith (1957)had the
advantage of being based on staged embryos. More recent compilations based on staged embryos have been
prepared by O’Rahilly and Boyden (19731, ORahilly
(19781, and O’Rahilly and Muller (1984). Despite these
previous studies, the manner in which the mesenchyma1 septum forms and thus separates the trachea and
esophagus during the critical period of stages 12 and 13
has not been fully understood. The present study was
undertaken to reexamine the septation of the respiratory and digestive tracts in Carnegie stages 12 and 13.
0 1994 WILEY-LISS, INC
MATERIALS AND METHODS
Materials for this study were obtained from the Carnegie Embryological Collection through the courtesy of
Dr. Ronan ORahilly, director of the Carnegie Laboratories (University of California, Davis). The 351 Carnegie embryos (CE) in good condition and prepared as
serial histologic sections of Carnegie stages 9 through
23 (Streeter, 1951; Heuser and Corner, 1957; O’Rahilly, 1973) were reviewed and photomicrographs prepared. In this study, particular attention was directed
to the 34 embryos in stages 12 and 13, which span the
period during which the tracheoesophageal septum appears. From these embryos, five were chosen for reconstruction based on their relevance to this study and on
the amount and condition of material available. The
following are the embryos selected for reconstruction.
Received June 4, 1993; accepted September 2, 1993.
Address reprint requests to Dr. Grover M. Hutchins, Department of
Pathology, The Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore,
MD 21287.
238
K.S. SUTLIFF AND G.M. HUTCHINS
Stage 12
Early Stage 12 (Fig. 1)
CE 8506, 3.7 mm crown-rump length (CRL), sectioned in the sagittal plane at 8 pm; CE 7852, 3.7 mm
CRL, sectioned transversely a t 10 pm; and CE 5923,
4.0 mm CRL, sectioned transversely at 10 pm.
A 3.7 mm CRL embryo (CE 85061, sectioned sagittally, was selected to illustrate the developing lung bud
at an early stage of septation. The lung bud consists of
a knoblike thickening of the endodermal wall of the
foregut and is growing outward in a ventral direction.
The ventral epithelium of the lung bud is three times
as thick as the dorsal epithelium of the foregut. Mesenchyme surrounds the lung bud and the other developing structures of the foregut. Inferior to the lung bud
is the developing liver diverticulum. The heart occupies the space ventral to the lung bud. The lung bud is
in the mesenchyme of the venous end of the dorsal
mesocardium (Bliss and Hutchins, 1992). The notochord is continuous with the endoderm of the pharyngeal region and is separated by intervening mesenchyme elsewhere. The notochord is also surrounded by
a column of sclerotomic cells, which are a trail of proliferating cells left behind as the somites grow dorsolaterally.
Three pairs of occipital somites are present. The first
occipital somite is not visible because it has begun to
undergo involution. Consequently, the rostralmost pair
seen is actually the second pair (Arey, 1920). The lung
bud is at the level of the fifth pair of somites.
The normal relationship of the digestive tube to the
whole embryo is shown in the upper right of Figure 1.
The embryonic body curvature reflects the beginning
of ventral flexion of the thoracolumbar region. The previous stage is characterized by a relatively straight
linear axis.
A frontal plane reconstruction of the lung bud area of
CE 7852 is shown in the lower left image of Figure 1.
The lung bud is also growing outward in a lateral direction. The level a t which the foregut and primitive
respiratory tract have a common lumen is within the
lower half of the foregut. The lumen of the foregut is
very narrow below the lung bud. It widens as it ascends
until it forms an oval at the level of the primitive pharynx just above the lung bud.
A groove, the longitudinal sulcus, is apparent along
the outside lateral wall and marks the transition point
between the thick epithelium of the lung bud and the
thin epithelium of the foregut. It runs inferior-ventrally from just above the lung bud to just below it. The
transition is gradual toward the primitive pharynx and
more abrupt at the base of the lung bud. The groove is
not apparent along the inside lateral wall, which appears smooth and projects slightly medially.
Stage 13
CE 9297, 4.5 mm CRL, sectioned sagittally at 8 pm;
and CE 5874, 4.8 mm CRL, sectioned transversely at
10 pm.
The foregut region was reconstructed to demonstrate
the developing structures of the digestive and respiratory systems. These structures included the lung bud,
trachea, esophagus, liver, and stomach. Surrounding
structures were also reconstructed to show their anatomic relationships. These structures included the neural tube, notochord, somites, heart, and mesenchymal
structures. The reconstructions were in the form of illustrations indicating development in left lateral, frontal, and median views.
Histologic sections for CE 8506, CE 9297, and CE
5923 had been photomicrographed for reconstruction.
Details of the photography have been described by Magovern et al. (1986). The negatives of each section were
projected through a Dokumater DL-2 Microfilm
Reader, and the specimens were traced. The developing
vertebral column and the body contour were utilized
for registration. Every section was traced in the area of
interest and approximately every other section on either side. The tracings were then stacked and superimposed for study with illumination from below. Composite drawings were made from the tracings to provide
left lateral views of the whole embryo. For a more detailed study of the developing respiratory and digestive
tracts, composite drawings were made of the foregut
region and surrounding structures. Structures that
overlay and obscured the composite image were traced
on separate sheets of paper while maintaining careful
registration (Gaunt, 1971).
For concise understanding of the growth and septation of the trachea and esophagus, median and frontal
plane projections were made from the tracings of CE
5923 and from xeroxed bromides of CE 7852 and CE
5874 (Payne and Hutchins, 1973). These projections
consisted of only the area of the foregut where the respiratory system develops.
Photomicrographs of the serial histologic sections of
embryos of stages 14 through 23, sectioned in the sagittal plane, from the Carnegie Collection and four fetuses from the Hopkins Pathology Collection, cut in the
median plane, were examined to determine the anatomic relationship of the tracheoesophageal septum to
the vertebral column. The four fetal specimens were of
80.0 mm, 125.0 mm, 185.0 mm, and 350.0 mm CRL.
RESULTS
The stage of appearance of selected anatomic features in 351 Carnegie embryos of stages 9 through 23
are listed in Table I. Most of these data have been previously published (Moore and Hutchins, 1981). The
lung bud and its primary branches, the right and left
mainstem bronchi, appear in stage 12.
Lafe Stage 12 (Fig. 2)
A 4.0 mm CRL embryo (CE 59231, sectioned transversely, was selected as being intermediate between
the first appearance of the lung bud observed in the
earlier stage 12 and the more advanced septation of the
trachea and esophagus seen in Stage 13.
The lung bud is more prominent and separation has
progressed. Two ridges of endodermal cells on the inside lateral wall join in the midline and take the form
of a saddle-shape fold, the tracheoesophageal sulcus.
Furthermore, the lung bud continues to grow ventrally
and bends downward into the mesenchyme ventral to
the foregut. The part of this mesenchyme that comes to
lie between the respiratory and digestive tubes consti-
239
TRACHEOESOPHAGEAL SULCUS
TABLE I. Stage of appearance of selected anatomic features in 351 normal human embryos'
Carneaie staae
Number of embryos
Crown-rump length*
Lung
Lung bud
Primary bronchi
Tracheal cartilage
Pulmonary vasculature
Pulmonary capillaries
One pulmonary vein
Pulmonary arteries
Two or more pulmonary
veins
Heart
Cardiac asymmetry
Septum primum
Ostium primum
Ostium secundum
Cardiac vasculature
Coronary capillaries
Coronary veins
Coronary arteries
Left superior vena cava
obliterated
Other
Parietal pericardium
Ribs
Sternum
Liver
Omental bursa
Spleen
Mesoneuhrosis
Metanephrosis
9
10
11
12
25
3
12
19
3.1
3.8
1.8 2.2
20.6 20.8 20.8 10.7
13
25
4.9
20.7
8 / 2 5 +
2125+
21125
17/25
14
45
6.5
10.9
15
16
17
31
38
29
9.7
12.4
7.8
21.1 11.5 21.2
18
32
15.0
21.5
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
35/45
+
+
+
+
19
20
19
17
18.4 20.8
11.5 21.4
+
+
+
5132 14119
10112+
+
+
7 / 2 5 +
7/25
+
+
+
+
+
+
+
+
+
+
+
33138 7/29
17130 30138 28129
+
+
5/45 24131
1/31 12138 27/29
+
+
+
+
+
+
+
+
1119 10117
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
16132
+
+
21
22
17
18
22.7 25.2
11.7 2 1.3
+
+
23
21
28.7
22.3
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
c
2117 10118 18121
1/38 20129 31132
+
1138 24129
6119+
13/24
19125
+
+
+
+
+
+
1/23 37145
+
+
+
+
+
+
+
+
+
+
+
+
2129
+
+
+
+
2/12 8/11
+ + +
+
+ +
+ +
27/32
+
+ +
+
+ + +
+
+
+ Feature present in all embryos examined; a blank space indicates that the feature was absent in all embryos examined.
* Mean + standard deviation.
tutes the tracheoesophageal septum. The superior mar- somite at which point it divides into the right and left
gin of the septum is at the level between the fifth and lung buds. The esophagus elongates and the distance
sixth somite. The anterior concavity of the thoracolum- between the lung bud and liver increases further. The
bar region has progressed further. The mesenchyme stomach is evident as a fusiform dilatation of the
between the foregut and the neural tube has increased. foregut.
A 4.8 mm CRL embryo (CE 5874), sectioned transThe distance between the lung bud and liver diverticversely and reconstructed in the frontal plane, was seulum has also increased.
The longitudinal sulcus, which was present on the lected to show the state of the developing lung bud. The
lateral outside wall of the 3.7 mm embryo, is evident. lung bud has lengthened caudally and has bifurcated
However, it is now also apparent on the inside lateral into the right and left lung buds. The left mainstem
bronchus is more in line with the trachea and is longer.
wall as a ridge of endodermal cells.
The longitudinal sulcus persists but now has an infeStage 13 (Fig. 3)
rior-posterior direction.
A 4.5 mm CRL embryo (CE 92971, sectioned sagitConfiguration of the Tracheoesophageal Sulcus (Fig. 4)
tally, was selected to show the separation of the traThree embryos (CE 7852, CE 5923, and CE 5874) are
chea and esophagus by the tracheoesophageal septum.
The esophagus and trachea become clearly evident in presented in a manner to show the configuration and
stage 13. The tracheoesophageal septum is 0.33 mm rapid growth and septation of the tracheoesophageal
in length (ORahilly and Tucker, 1973). Below the sep- area. The dotted line indicates the level of the top of the
tation point, the lumen of the esophagus narrows sig- tracheoesophageal sulcus, which remains constant relnificantly, almost to the point of occlusion. There is ative to vertebral structures as the lung bud grows
also marked narrowing directly above the septation caudally.
Figure 4A shows left lateral reconstructions of three
point until reaching the pharynx where the lumen widens. Figure 3 also shows the septation point to be at the embryos in which the longitudinal sulcus described
level between the fifth and sixth somite. The lung bud above is clearly evident. In Figure 4B, left lateral rehas descended to the level of the seventh and eighth constructions cut in the median plane are shown. The
-
240
K.S. SUTLIFF AND G.M. HUTCHINS
\
Lung
bud
ml
'Neural t u b e
Notochord
Mesenchyme
FRONTAL VIEW
'
0.1 mm'
Fig. 1. Two Carnegie embryos show the developing lung bud as a
ventral outgrowth of the foregut. The left lateral median plane reconstruction of the foregut and adjacent structures are from CE 8506,
sections 41215 through 4 / 3 4 . The dorsal aorta is not depicted in order
to obtain a n unobstructed view of the foregut. The normal relationship of the digestive tube (indicated by a dotted line) to the whole
embryo is shown in the upper right. The image in the lower left is a
frontal plane reconstruction of the lung bud region from CE 7852,
sections 2/1/13through 21317. The level at which the foregut and primitive respiratory tract have a common lumen is marked by ( + ). Liv,
liver diverticulum; LA, left atrium, LV, left ventricle; SV, sinus venosus.
TRACHEOESOPHAGEAL SULCUS
24 1
-
FRONTAL VIEW
0.1 mm
Tracheoesophageal sulcus
Fig. 2. Carnegie embryo 5923 shows the progression of the developing lung bud and the septation of the respiratory and digestive
tracts. The left lateral median plane reconstructions (upper right and
center) are based in part on reconstruction drawings in Streeter
(1942, Fig. 2, xii). The upper right image shows the normal relationship of the digestive and early respiratory tract (indicated by a dotted
line) to the whole embryo. Within the center image, the cut median
plane view through the lung bud region is a lateral reconstruction of
sections 11615 through 211112. A saddle-shape fold, the tracheoesophageal sulcus (*), is evident. In addition, the tracheoesophageal septum
(Te sept) makes its first appearance. The dorsal aorta is not depicted
in order to obtain an unobstructed view of the foregut. The image in
the lower left is a frontal plane reconstruction from sections 11615
through 211112 of the lung bud region. The level at which the digestive
and respiratory tubes have a common lumen is marked by ( + 1. Te
sept, tracheoesophageal septum; Gb, gallbladder.
242
K.S. SUTLIFF AND G.M. HUTCHINS
Stage 13
\
Dorsal aorta
Esophagus
'0.1 mm
I
I
Fig. 3. Two Carnegie stage 13 embryos show the progressive septation of the trachea and esophagus. The left lateral median plane reconstructions are from CE 9297, sections 31111 through 51315. The
normal relationship of the digestive and respiratory tube (indicated
by the dotted line) to the whole embryo is shown in the upper right.
The image in the lower left is a frontal plane reconstruction of the
lung bud region from CE 5874,sections 51314 through 61411.The level
at which the trachea and esophagus have a common lumen is marked
by ( + ). Dp, dorsal pancreas; Gb, gallbladder; St, stomach.
243
TRACHEOESOPHAGEAL SULCUS
Early Stage 12
Late Stage 12
Stage 13
Fig. 4. Reconstructions of the lung bud and foregut from three Carnegie embryos summarize the rapid progression of the tracheoesophageal area in stages 12 and 13.The arrows describe the configuration
of the tracheoesophageal sulcus by convex or negative (B) and concave
or positive (C) curvatures. The early stage 12 column is based on a
reconstruction of CE 7852, sections 211113 through.21317. The late
stage 12 column is based on a reconstruction of CE 5923, sections 11615
through 211112 and the stage 13 column is based on a reconstruction
of CE 5874, sections 51314 through 61411. The dotted line through each
stage indicates the level between somites 5 and 6.
formation of the tracheoesophageal sulcus is evident. It
begins as a slight convex curve in a dorsal-ventral direction when the lung bud begins to protrude in early
stage 12. It progresses to a curvature that is convex
cranially in late stage 12 and becomes more accentu-
ated in stage 13. In Figure 4C, frontal reconstructions,
cut just anterior to the foregut in stage 12 and the
esophagus in stage 13, are shown. In this view, the
tracheoesophageal sulcus has the form of a curved surface, which in the coronal plane is concave in the cra-
244
K.S. SUTLIFF AND G.M. HUTCHINS
Fig. 6. The static position of the tracheoesophageal sulcus. A hemisected 350.00 mm CRL fetus of the Hopkins Pathology Collection
shows the top of the tracheoesophageal septum to be a t the level of the
first cervical vertebra, as indicated by the line.
Fig. 5.The static position of the tracheoesophageal sulcus. A sagittally sectioned normal human embryo of the Carnegie Collection.
Section 26/112 of a stage 23 embryo (CE 5422) shows the top of the
tracheoesophageal septum to be at the level of the first cervical vertebra, as indicated by the line.
nial direction and in the sagittal plane is convex in the
cranial direction.
ure 6 show that the top of the tracheoesophageal septum remains at the level of the first cervical vertebra
throughout prenatal life.
DISCUSSION
An understanding of the normal septation of the human respiratory and digestive tracts, which begins in
Static Position of the Tracheoesophageal Sulcus
Carnegie stage 12, may help to suggest the cause of
(Figs. 5 and 6)
abnormal septation leading to the malformations
Examination of sections from the approximate me- esophageal atresia and tracheoesophageal fistula. In
dian plane of embryos of stages 14 through 23 showed normal septation a mesenchymal structure, the trachethe progressive increase in length of the tracheoesoph- oesophageal septum, separates the digestive and respiageal septum. The right and left lung buds, now re- ratory tubes shortly after the appearance of the lung
ferred to as primary bronchi, curve dorsally around the bud (O’Rahilly and Muller, 1984). In the pathologic
esophagus. The first indication of the primitive larynx condition, tracheoesophageal fistula, a persistent comis visible, as an inlet, with the appearance of the hy- munication connects the trachea and esophagus and is
popharyngeal eminence, arytenoid swellings, and epi- usually associated with esophageal atresia. These abthelial lamina. The epithelial lamina is a t the level of normalities occur in several forms and a t present there
somite 5 (ORahilly and Muller, 1984). The atlas ((31) is no agreement as to their cause (Smith, 1957; O’Racan be used to identify the site of somite 5 since scle- hilly and Muller, 1984). Understanding the pathogenrotome 5 gives rise to the neural arch of the atlas. The esis of esophageal atresia and tracheoesophageal fispoint at which the trachea and esophagus separate re- tula requires an understanding of the mechanics of
mains at the levels of somites 5 and 6, which corre- normal development of these structures.
The morphologic observations presented here in responds to the tip and base of the dens of the second
cervical vertebra and the centrum of the first cervical gard to the septation of the respiratory and digestive
vertebra (Muller and O’Rahilly, 1986). The stage 23 tracts are consistent with those of previous studies. The
embryo in Figure 5 and the 350 mm CRL fetus in Fig- respiratory system makes its first appearance at stage
245
TRACHEOESOPHAGEAL SULCUS
Catem
1
Catenoid:
surface of revolution of a
R,
= -R,
Net zero curvature
Catenoidal
tulcus
Lung bud
Fig. 7.Diagram illustrating the generation of a catenoid from rotation of a catenary and the catenoidal configuration of the tracheoesophageal sulcus. The orthogonal radii (R) of curvature at every
point are equal but opposite in direction (R, = -RJ. Thus every point
on a catenoid has net zero curvature. This property of zero curvature
determines that pressure differences between the two sides of the
surface will not affect tension since the curvature is zero (P = T (l/ri,
+ l/rout).Similarly, tension in the surface will have no effect on
pressure in the surroundings.
10 as a widened terminal portion of the laryngotracheal sulcus known as the respiratory primordium. By
the end of stage 11,the respiratory primordium is characterized by a knoblike thickening of the endodermal
wall, which will become the lung bud. During stage 12,
the lung bud appears and separation of the respiratory
and digestive tracts begins. With growth, the lung bud
becomes more prominent and bends downward into the
mesenchyme ventral to the foregut. The part of this
mesenchyme that comes to lie between the respiratory
and digestive tubes constitutes the tracheoesophageal
septum. Smith (1957) describes septation by the union
of proliferating endodermal ridges from the lateral
wall of the foregut. Later studies by O’Rahilly and Boyden (1973), O’Rahilly and Tucker (1973), and O’Rahilly
(1978) support these findings. A more recent study by
O’Rahilly and Muller (1984) support and enhance the
earlier work. They describe a longitudinal sulcus (the
Grenzfurche), where thin epithelium runs into thicker
epithelium and is visible externally. The longitudinal
sulcus apparently indicates the subsequent line of separation between the respiratory and digestive tracts
(Davis, 1923).These observations are supported by this
study. However, previous studies have not made it
clear that the endodermal ridges described by Smith
(1957) and the longitudinal groove described by O’Rahilly and Muller (1984) take the form of a saddle-
shape fold, the tracheoesophageal SU~CUS,
as they unite
caudally to divide the foregut into respiratory and digestive portions. This sulcus appears to be crucial to
the formation of the tracheoesophageal septum and,
therefore, to the normal septation of the trachea and
esophagus.
As in the present study, the study by ORahilly and
Muller (1984) also found that the cranial end of the
septum remains static relative to vertebral structures
while the lung bud and trachea descend. The location of
somites and vertebrae remain relatively stable during
embryonic development. Therefore, as emphasized by
Muller and ORahilly (19861,failure to use the vertebral column as a reference has resulted in the commonly held, but incorrect, view that the tracheal bifurcation remains a t a constant level in the embryo, while
the septation point ascends. The septation point is the
summit of the mesenchymal septum, and it is this area
that remains at the level between somites 5 and 6 , the
future first cervical vertebra.
The configuration of the tracheoesophageal sulcus
appears to account for both the development of the tracheoesophageal septum and the static position of its
top. As shown diagrammatically in Figure 7, the sulcus
has a catenoidal configuration. Catenoidal structures
remain static during development in contrast to spherical or tubular structures which grow, expand, and
246
K.S. SUTLIFF AND G.M. HUTCHINS
Sphere:
surface of revolution
of a semi-circle
R, = R,
Two positive
curvatures
Spherically
0
1
I
" N w
Fig. 8. Diagram illustrating the generation of a sy :re from rotation
of a semicircle and the spherical configuration of the lung bud. The
orthogonal radii (R) of curvature are equal and of the same direction
(R, = RJ. Every point of a sphere has a net curvature. This property
of net curvz ire determines that a pressure difference between the
two sides of the surface will change tension in the surface. Similarly,
tension development in the surface will exert pressure on the surroundings.
lengthen (Fig. 8). A catenoidal configuration has been
suggested to be of importance in studies of sulci and
saddle-shape folds in the developing heart (Magovern
et al., 1986;Hutchins et al., 1979;Meredith et al., 1979;
Kundmueller and Hutchins, 1990). The growth-limiting properties of the atrioventricular, interventricular,
outflow tract, and interatrial sulci appear crucial in
determining cardiac septation and the correct alignment of the components of the developing heart.
A catenoid is the surface of rotation of a catenary,
which is a natural curvature that can be represented
by the curve of repose of a suspended chain. The surface
of a catenoid has the property of having orthogonal
radii of curvature a t every point that are equal but
opposite in direction and thus sum to zero (Thompson,
1942).As a result of its net zero curvature, the catenoid
surface may have a pressure differential between its
two sides, but this pressure difference does not change
tension in the surface. This property is a reflection of
the Laplace relationship where pressure equals tension
times curvature. Similarly, tension produced within a
catenoidal surface will not affect the pressure of its
surroundings. However, surfaces that do not have a net
zero curvature are subject to expansion or extension as
a result of pressure differences between the two sides of
the surface. In other words, a pressure difference between the two sides of a curved surface will produce
tension in the structure and tension development in
the structure produces a pressure difference in the surroundings. In the development of the respiratory system, a sulcus with a catenoidal configuration may have
different potential for growth and expansion than adjacent areas that have outwardly convex curvatures
such as the spherically shaped lung bud shown in Figure 5. Whereas catenoidal properties would maintain
the position of the sulcus, the adjacent convex or positive curvatures of the lung bud would permit expansion
and growth.
In conclusion, the relative lack of growth in the saddle-shape fold of the tracheoesophageal sulcus, in contrast to the rapid growth of the convex components of
the lung bud, is attributable to the different mechanical properties of the two configurations. The normal
development of the tracheoesophageal septum appears
to depend on this saddle-shape fold. The observations
made here suggest that the origin of tracheoesophageal
malformations should be sought in a configurational
abnormality arising in Carnegie stage 12.
LITERATURE CITED
1. Arey, L.B. 1920 The history of the first somite in human embryos.
Contrib. Embryol. Carnegie Inst. Wash., Washington, D.C., 11:
61-900.
2. Bliss 11, D.F., and G.M. Hutchins 1993 The dorsal mesocardium
and development of the pulmonary veins in human embryos. Am
J Cardiovasc Pathol (in press).
3. Davis, C.L. 1923 Description of a human embryo having twenty
TRACHEOESOPHAGEAL SULCUS
paired somites. Contrib. Embryol. Carnegie Inst. Wash., Washington, D.C., 15:25-27.
4. Gaunt, W.A. 1971 Microreconstructions. Pitman, London.
5. Heuser, C.H., and G.W. Corner. 1957 Developmental horizons in
human embryos: Description of age group X, 4 to 12 somites.
Contrib. Embryol. Carnegie Inst. Wash., Washington, D.C., 36:
29-39.
6. Hutchins, G.M., L. Liebman, G.W. Moore, and F. Gharagozloo
1979 Atrioventricular canal malformations interpreted as secondary to reduced compression upon the developing heart. Am. J .
Pathol., 95579-595.
7. Keibel, F., and F. P. Mall 1912 Manual of Human Embryology.
Lippincott, Philadelphia, pp. 291-482.
8. Kundmueller, M., and G.M. Hutchins. 1990 The right outflow
tract sulcus in embryonic human hearts. Am. J. Cardiovasc.
Pathol., 3:291-299.
9. Magovern, J.H., G.W. Moore, and G.M. Hutchins 1986 Development of the atrioventricular valve region in the human embryo.
Anat. Rec., 215:167-181.
10. Meredith, M.A., G.M. Hutchins, and G.W. Moore 1979 Role of the
left interventricular sulcus in formation of the interventricular
septum and crista supraventricularis in normal human cardiogenesis. Anat. Rec., 194:417-428.
11. Moore, G.W., and G.M. Hutchins 1981 Symbolic logic analysis of
congenital heart disease. Pathol. Res. Pract., 171:59-85.
12. Muller, F., and R. O’Rahilly 1986 Somitic-vertebral correlation
and vertebral levels in the human embryo. Am. J. Anat., 177:319.
13. ORahilly, R. 1973 Developmental Stages in Human Embryos.
Part A: Embryos of the First Three Weeks (Stages 1 to 9). Reprint
631. Carnegie Inst. Wash., Washington, D.C.
247
14. ORahilly, R. 1978 The timing and sequence of events in the development of the human digestive system and associated structures during the embryonic period proper. Anat. Embryol., 153:
123-136.
15. ORahilly, R., and E.A. Boyden 1973 The timing and sequence of
events in the development of the human respiratory system during the embryonic period proper. Z. Anat. Entwick1.-Gesch., 141:
237-250.
16. ORahilly, R., and F. Muller 1984 Respiratory and alimentary
relations in staged human embryos. New embryological data and
congenital anomalies. Ann. Otol. Rhinol. Laryngol., 93:421-429.
17. ORahilly, R., and J.A. Tucker 1973 The early development of the
larynx in staged human embryos. Part 1:Embryos of the first five
weeks (to stage 15). Ann. Otol. Rhinol. Laryngol., 82 (Suppl.7):
1-27.
18. Payne, K.T., and G.M. Hutchins 1973 Rapid production of reconstruction drawings from serial sections. Am. J. Clin. Pathol., 60:
820-822.
19. Smith, I.E. 1957 The early development of the trachea and esophagus in relation to atresia of the esophagus and tracheoesophageal fistula. Reprint 245. Contrib. Embryol. Carnegie Inst.
Wash., Washington, D.C., 36:41-57.
20. Streeter, G.L. 1942 Developmental horizons in human embryos:
Description of age group XI, 13 to 20 somites, and age group XII,
21 to 29 somites. Reprint 541. Contrib. Embryol. Carnegie Inst.
Wash., Washington, D.C., 30:211-245.
21. Streeter, G.L. 1951Developmental Horizons in Human Embryos:
Age Groups XI to XXIII. Carnegie Inst. Wash., Lord Baltimore
Press, Washington, D.C.
22. Thompson, DA.W. 1942 On Growth and Form, 2nd ed. Macmillan, New York, pp. 365-384.