Paper - The development of the mucous membrane of the large intestine and vermiform process in the human embryo: Difference between revisions

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| | [[File:Mark_Hill.jpg|90px|left]] This historic 1910 paper by Franklin Paradise Johnson (1888-1943) describes the development of the  mucous membrane of the large intestine and vermiform process in the human embryo.
| | [[File:Mark_Hill.jpg|90px|left]] This historic 1913 paper by Franklin Paradise Johnson (1888-1943) describes the development of the  mucous membrane of the large intestine and vermiform process in the human embryo. In this paper he describes embryos and wax models from the [[Harvard Collection|Harvard Embryological Collection]].  
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Other papers by this author: {{Ref-Johnson1910b}}  
Other papers by this author: {{Ref-Johnson1910b}}  
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Twenty-Nine Figures
Twenty-Nine Figures


The following paper is .the second of a series of studies concerning the mucous membrane of the digestive tract. The
The following paper is .the second of a series of studies concerning the mucous membrane of the digestive tract. The first (Johnson ’lO) dealt with the development of the oesophagus, stomach and small intestine. The present paper is devoted entirely to the large intestine, and includes all its parts except the lower portion of the rectum. It is followed by an account of the effects of distention upon the small and large intestines of various animals. It is proposed to publish later an account of the development of the anal portion of the rectum, work upon which is nearly completed. The study of the mucous membrane of the digestive tract was proposed to me by Dr. F. T. Lewis in 1909, and as the work has progressed, I have received from him many valuable suggestions.
first (Johnson ’lO) dealt with the development of the oesophagus, stomach and small intestine. The present paper is devoted
entirely to the large intestine, and includes all its parts except
the lower portion of the rectum. It is followed by an account
of the effects of distention upon the small and large intestines
of various animals. It is proposed to publish later an account
of the development of the anal portion of the rectum, work upon
which is nearly completed. The study of the mucous membrane of the digestive tract was proposed to me by Dr. F. T.
Lewis in 1909, and as the work has progressed, I have received
from him many valuable suggestions.


The development of the large’ intestine is of special interest
The development of the large’ intestine is of special interest owing to the variety of pictures its mucosa presents. Relatively simple in the beginning and again in the adult as compared with other portions of the alimentary canal, the mucosa passes through a number of complicated changes before it attains its full development. To begin with, the smooth epithelial tube of the large intestine develops more or less regular longitudinal folds. These folds, as will be subsequently described, are later replaced by villi. Still later the villi themselves disappear. Meanwhile, glands are forming, and when the villi have entirely faded out, the large intestine reaches its adult condition. The presence of ‘transitory’ villi has long been known, being first described by Barth in 1868. Since then they have been studied by a number of investigators, and several opinions have arisen in regard to their manner of disappearance. However, most of the former work has been done on lower animals, no one account giving a complete history of the changes that take place in the human embryo.
owing to the variety of pictures its mucosa presents. Relatively
simple in the beginning and again in the adult as compared with
other portions of the alimentary canal, the mucosa passes through
a number of complicated changes before it attains its full development. To begin with, the smooth epithelial tube of the large
intestine develops more or less regular longitudinal folds. These
folds, as will be subsequently described, are later replaced by
villi. Still later the villi themselves disappear. Meanwhile,
glands are forming, and when the villi have entirely faded out,


187
188 FRANKLIN PARADISE JOHNSON


the large intestine reaches its adult condition. The presence of
In the present paper an attempt is made to describe in some detail the mucosa of the large intestine and vermiform process in a number of consecutive embryonic stages, and to present a series of pictures made from wax reconstructions illustrating the descriptions. The following account deals strictly with the human embryo, and is based on a number of carefully selected stages. The embryos used are arbitrarily divided into two groups ;—the younger stages, which were sectioned whole; and the older stages, from which the various portions of the digestive tube were removed from the embryo and sectioned separately. The younger stages used were all obtained from the [[Harvard Collection|Harvard Embryological Collection]]. They are as follows:
‘transitory’ villi has long been known, being first described by
<br>
Barth in 1868. Since then they have been studied by a number
{{Johnson1913table1}}
of investigators, and several opinions have arisen in regard to
<br>
their manner of disappearance. However, most of the former
The older stages were obtained from three different collections. I Wish here to express my thanks to Prof. C. S. Minot, Harvard Medical School, Prof. C. M. Jackson, University of Missouri, and Prof. Franz Keibel, Freiburg i/Br., for allowing me the privilege of cutting out what portions of their embryos I desired for my work. The list of older stages used is as follows:
work has been done on lower animals, no one account giving a
<br>
complete history of the changes that take place in the human
{{Johnson1913table2}}
embryo.
<br>
 
==The Large Intestine==
 
===Early development===
 
In an embryo of 7.5 mm. the large intestine, like the oesophagus, stomach, and small intestine of the same embryo‘, is a simple tube of epithelium surrounded by mesenchyma. It is continuous, without demarction, with the small intestine above, and with the urogenital sinus below. Its cephalic end is indistinctly indicated by a slight swelling, which is regarded by Lewis (’11) as the beginning of the Vermiform process. This swelling, which I will designate by the term ‘colic ampulla’ (ampulla coli), is spindle-shaped and has a diameter (measured from side to side in its widest place) of 0.07 mm. Below the swelling the tube becomes markedly narrower. In its narrowest portion it measures but 0.04 mm. in diameter. As the urogenital sinus is approached the epithelial tube again increases in size and becomes compressed from side to side. This enlargement passes insensibly over into the epithelium of the cloaca.
 
 
The walls of the epithelial tube also vary in thickness. Above, where it is broadest, the walls have a thickness of about 0.028 mm. and are composed of cells which have no distinct cell boundaries. Three rows of oval nuclei are discernible. In the narrower middle portion the walls average about 0.017 mm. in thickness, and show only two rows of nuclei. Where the tube is expanded in the cloacal region, the epithelium is approximately of the same thickness as in the colic ampulla. The lumen in most places is a narrow slit-like cleft, larger in the extremities than in the rnid—region of the large intestine, but everywhere present and patent. It communicates with the larger lumen of the cloaca, but cannot be traced through this to the outside because of the presence of the cloacal membrane.
 
 
In an embryo of 10 mm. the large intestine presents practically the same relations, but shows a marked increase in size. The colic ampulla, which is now situated well out in the coelom of the umbilical cord, measures alout 0.33 mm. in diameter, and has an epithelium 0.045 mm. in thickness. A slight budlike protuberance of almost the same size as the swelling itself, arises from it, and extends into the mesenchyma. Followed caudally, the epithelial tube of the large intestine quickly diminishes in size, and continues of small size until the region of the rectum is reached. Here it presents another spindle—shaped swelling. This swelling is connected with the cloaca by a short and narrow tube. The upper narrow portion of the epithelial tube measures about 0.07 mm. in diameter, and its wall is 0.028 mm. thick. The swelling is’ 0.12 mm. in diameter, and has a wall thickness of 0.036 mm. The lumen is continuous as far as the cloacal membrane where it is closed ofi“ from the exterior.
 
At 16 mm. the colic ampulla is similar in form but larger than in the preceding stages, being now 0.17 mm. in diameter. It
 
is directly continued into the Vermiform process, which is found in the umbilical cord, pointing away from the embryo. Large at its base where it joins the colic ampulla, the vermiform process tapers gradually towards its blind end. The before-mentioned narrow portion of the large intestine, now 0.09 mm. in diameter, has increased much in length. The lumen of the lower end of the digestive tube no longer leads into the cloaca, but opens to the outside by an extremely small aperture.
 
In the further course of its development, the swelling in the rectal region becomes much larger, and longitudinal folds make their appearance. These longitudinal folds increase in numbers, and are markedly constant in position in all the older stages. Just what is the fate of these folds I am unable at the present time to state precisely, but it is not improbable that they give rise to the rectal columns (columnae rectales Morgagni) while the spaces between them no doubt develop into the rectal sinuses (sinus rectales). A discussion of the further development of this portion of the digestive tract, however, has been omitted from the present paper.
 
The development of longitudinal folds


In the present paper an attempt is made to describe in some
In an embryo of 22.8 mm. one sees for the first time a change in the form of the epithelium. In the colic ampulla, which now has a diameter of 0.20 mm., the epithelium shows three low longitudinal ridges on its inner surface. These ridges also extend for short distances into the colon and vermiforrn process.
detail the mucosa of the large intestine and vermiform process
in a number of consecutive embryonic stages, and to present a
series of pictures made from wax reconstructions illustrating
the descriptions. The following account deals strictly with the
human embryo, and is based on a number of carefully selected
stages. The embryos used are arbitrarily divided into two
groups ;—the younger stages, which were sectioned whole; and
the older stages, from which the various portions of the digestive tube were removed from the embryo and sectioned separately. The younger stages used were all obtained from the
Harvard Embryological Collection. They are as follows:


CROWN-RUM? LENGTH H.E.C. SERIES NO. FIXATION
It becomes necessary at this point to explain the manner in which the terms ‘ridges’ and ‘folds’ have been used throughout the remainder of this article. The term ‘ridge’ has been employed to designate a thickening of the epithelium which projects into the lumen. It must have no corresponding indentation on its under surface into which mesenchyma would extend. By a ‘fold’ is meant a projection with an indented basal surface, into which the underlying mesenchyma protrudes. This distinction is desirable, as its usage makes it possible to explain in few words the shape of the basal surface of the epithelium along with that of its free surface.  


mm.


7.5 256 Zenker’s fluid
The epithelium in the embryo under consideration (22.8 mm.) varies in thickness in different regions. In the colic ampulla and vermiform process it is 0.056 mm. thick and shows three to four rows of nuclei. In the remainder of the colon down to the rectal ampulla, it is only 0.034 mm. in thickness and shows but two to three rows of nuclei. At no place are the boundaries between the cells distinct, but the free and basal surfaces are well marked.
10.0 1000 Zenker’s fluid
16 .0 1322 Picro-sulphuric
22.8 871 Alcohol and formalin
30.0 913 Formalin
37.0 820 Parker’s fluid
42.0 838 Zenker’s fluid


The older stages were obtained from three different collec~
In an embryo of 30 mm. the whole of the vermiform process and the valve of the colon lie in the coelom of the umbilical cord. An examination of the interior of the colon in this region shows the beginnings of two to three epithelial ridges. These Vary in height, the epithelium being 0.070 mm. thick, measured through the summit of the largest ridge, while in the depressions between them, it is only about 0.028 mm. thick. Three or four rows of nuclei can be made out. The remainder of the colon has an average diameter of 0.15 mm. Throughout its great length the epithelial tube is still cylindrical in shape, having a wall 0.048 mm. in.thickness. Three or four rows of nuclei are present.
tions. I Wish here to express my thanks to Prof. C. S. Minot,
Harvard Medical School, Prof. C. -M. Jackson, University of
Missouri, and Prof. Franz Keibel, Freiburg i/Br., for allowing
me the privilege of cutting out what portions of their embryos
I desired for my work. The list of older stages used is as follows:
DEVELOPMENT OF THE LARGE INTESTINE 189


CROWN-RUkfP LENGTH FIXATION COLLECTION SERIES N0.
At 37' mm. the whole of the vermiform process still lies in the umbilical cord. The epithelial ridges are higher than in the former stages. In the base of the vermiform process there are four of these, in the middle only three; in the beginning of the colon, three or four. The highest ridge measures about 0.10 mm. in height and has three or four rows of nuclei. Between the ridges the epithelium is only 0.042 mm. thick and shows but two or three nuclear layers. The remainder of the large intestine gradually decreases in size when followed caudally. The portion which is to become the ascending colon is 0.27 mm. in diameter; the transverse 0.22 mm.; and the descending colon 0.18 mm. The epithelium is about 0.056 mm. thick in all these portions. A few vacuoles, such as have been found in the epithelial walls of the stomach and oesophagus are present in the colon of this embryo.
mm.
50 Zenker’ s fluid Keibel
55 Alcohol Minot 249
58 Zenker’ s fluid Keibel
65 Zenker’s fluid Keibel
70 Alcohol Keibel
73 Picro-sulphuric Minot 116
75 Alcohol Minot 110
88 Formalin Jackson 137
99 Alcohol Xlinot 340
1 10 Fcrmalin Jackson 143
120 Zonker’ s fluid Vlinot 342
140 Formalin Jackson 263
170 Formalin Jackson 222
187 Formalin _VIinot 315
190 Formalin Jackson
200 Formalin Jackson 89
240 M1‘1ller’s fluid Viinot 186
320 Formalinl Jackson 16
Birth” . . . . . . . . , . . . . . Zenker’s fluid Minot 345
Birth3 . . . . . . . . . . . . . . Zenker’s fluid Vlinot 341
Two weeks child4. . . Zenker’s fluid Vlinot


1 First injected with a mixture of phenol, alcohol, glycerino, and formalin
2 Premature birth at seven (?) months. Lived thirty minutes


3 Normal fetus at birth
In an embryo of 42 mm. the ridges of the epithelium are in part replaced by true longitudinal folds. In the Vermiform process and ascending colon three to four of these are present; in the transverse colon two to three; in the greater part of the descending colon three; while in the remainder of the descending colon five to six more irregular ones. These folds vary in height from 0.014 to 0.028 mm. The epithelium is thicker on their crests than between them. It presents an appearance which is largely in accordance with a condition which Patzelt (’83) has found in the large intestine of the cat embryo. He describes two types of cells. In the corners of the star-shaped lumen the cells are short and broad, and have basal nuclei which stain intensely with haemotoxylin. The cells of the ‘second type are found on the tops of the folds. They are longer, finely granular, and somewhat denser. Their nuclei are long—oval or drop-shaped and stain more intensely than those of the first type. The for~ mer groups of cells he states are the first anlagen of the Lieberkiilin glands; the latter of the villi. The epithelium of the large intestine of the embryo under consideration (42 mm.) has been described and pictured by Lewis (’11). The two types of cells are found arranged in separate groups, but, however, are not as distinct as those of the cat described by Patzelt.
4 Premature at seven months. Lived two weeks


THE LARGE INTESTINE
Early development


In an embryo of 7.5 mm. the large intestine, like the oesophagus, stomach, and small intestine of the same embryo‘, is a
In the ascending colon of an embryo of 50 mm., the epithelial tube has a diameter of about 0.23 mm., and shows four distinct longitudinal folds. These are, as shown in figure 12, rounded on their tops, and are of different heights, the largest measuring about 0.06 mm. In the piece of ascending colon sectioned for study, which measures about 0.7 mm. in length, the epithelial tube changes but little in shape, the four distinct longitudinal folds running throughout. The epithelium, which has an aVer~ age thickness of 0.050 mm., is columnar, and, as seen in sections ten microns thick, is apparently stratified, being composed of two or perhaps three, layers of cells. The nuclei, which are oval in shape, are all placed in a zone midway between the free and basal surfaces of the epithelium, there being a clear zone of protoplasm on either side. A definite cuticular border is everywhere present on the free surface of the epithelium. Two distinct types of cells are not visible. Outside of the epithelium is a zone of loose mesenchyma which is bounded by a thin layer of myoblasts, the circular layer of the muscularis. This is in turn bounded by a layer of mesenchyma and surrounding the whole, except at its mesenteric attachment, a distinct serous epithelium is seen.
simple tube of epithelium surrounded by mesenchyma. It is
continuous, without demarction, with the small intestine above,
and with the urogenital sinus below. Its cephalic end is indistinctly indicated by a slight swelling, which is regarded by Lewis
(’11) as the beginning of the Vermiform process. This swelling,
which I will designate by the term ‘colic ampulla’ (ampulla
coli), is spindle-shaped and has a diameter (measured from side
to side in its widest place) of 0.07 mm. Below the swelling the
tube becomes markedly narrower. In its narrowest portion it
190 FRANKLIN PARADISE JOHNSON


measures but 0.04 mm. in diameter. As the urogenital sinus
is approached the epithelial tube again increases in size and
becomes compressed from side to side. This enlargement passes
insensibly over into the epithelium of the cloaca.


The walls of the epithelial tube also vary in thickness. Above,
In passing ab-orally from the ascending colon into the transverse colon, one of the four longitudinal folds just described drops out, while a second becomes so much reduced in size that it is scarcely recognizable as a fold (figs. 1 and 13). The two remaining folds are distinct andabout 0.06 mm. in height. The epithelial tube has a diameter of about 0.27 mm. The remaining features of this portion of the large intestine are similar to those of the ascending colon.
where it is broadest, the walls have a thickness of about 0.028
mm. and are composed of cells which have no distinct cell boundaries. Three rows of oval nuclei are discernible. In the narrower middle portion the walls average about 0.017 mm. in
thickness, and show only two rows of nuclei. Where the tube
is expanded in the cloacal region, the epithelium is approximately
of the same thickness as in the colic ampulla. The lumen in
most places is a narrow slit-like cleft, larger in the extremities
than in the rnid—region of the large intestine, but everywhere
present and patent. It communicates with the larger lumen
of the cloaca, but cannot be traced through this to the outside
because of the presence of the cloacal membrane.


In an embryo of 10 mm. the large intestine presents practically the same relations, but shows a marked increase in size.
===First appearance of goblet cells===
The colic ampulla, which is now situated well out in the coelom
of the umbilical cord, measures alout 0.33 mm. in diameter,
and has an epithelium 0.045 mm. in thickness. A slight budlike protuberance of almost the same size as the swelling itself,
arises from it, and extends into the mesenchyma. Followed
caudally, the epithelial tube of the large intestine quickly diminishes in size, and continues of small size until the region of the
rectum is reached. Here it presents another spindle—shaped
swelling. This swelling is connected with the cloaca by a short
and narrow tube. The upper narrow portion of the epithelial
tube measures about 0.07 mm. in diameter, and its wall is
0.028 mm. thick. The swelling is’ 0.12 mm. in diameter, and
has a wall thickness of 0.036 mm. The lumen is continuous
as far as the cloacal membrane where it is closed ofi“ from the
exterior.


At 16 mm. the colic ampulla is similar in form but larger than
In the iliac colon (50 mm. embryo), the epithelial tube as a whole is flattened from side to side. Its greater diameter is 0.36 mm., its lesser 0.18 mm. A considerable change in the condition of folds is evident. They are shallow, irregular, and more numerous than in the ascending and transverse colons. A model of a small portion of this region is shown in figure 14. The distinction between epithelial ridges and folds is here apparent——only those protuberances, which have indented basal surfaces into which the mesenchyma extends, being considered as true folds. Measured through the ridges the epithelium is in places 0.084 mm. thick, while in the clefts between them, it is only 0.028 mm. thick. The two types of cells described by Lewis in the 42 mm. stage are distinct. A few cells on the ridges have a protoplasm .which is clearer than others, and are shaped somewhat like goblet cells. Because these cells in the next few stages take on more and more the appearance of goblet cells until their identity cannot be doubted, I believe them to be goblet cells in a very early stage of differentiation. Voigt (’99) was able to distinguish goblet cells first in the rectum of a human embryo of 70 mm.
in the preceding stages, being now 0.17 mm. in diameter. It


is directly continued into the Vermiform process, which is found
DEVELOPMENT or THE LARGE INTESTINE 191


in the umbilical cord, pointing away from the embryo. Large
The ascending colon of an embryo of 55 mm. has a diameter’ of 0.45 mm. Ten to twelve longitudinal ridges are found, but distinct folds are absent. The ridges are irregular in form and of varying size, the largest being about 0.10 mm. in height. The two types of cells are distinct now in this region of the large intestine, some of which are like those which Patzelt has described as drop-shaped. In many places large vacuoles similar to those described above are found in the epithelium of the ridges.
at its base where it joins the colic ampulla, the vermiform process
tapers gradually towards its blind end. The before-mentioned
narrow portion of the large intestine, now 0.09 mm. in diameter, has increased much in length. The lumen of the lower end
of the digestive tube no longer leads into the cloaca, but opens
to the outside by an extremely small aperture.


In the further course of its development, the swelling in the
rectal region becomes much larger, and longitudinal folds make
their appearance. These longitudinal folds increase in numbers,
and are markedly constant in position in all the older stages.
Just what is the fate of these folds I am unable at the present
time to state precisely, but it is not improbable that they give
rise to the rectal columns (columnae rectales Morgagni) while
the spaces between them no doubt develop into the rectal sinuses
(sinus rectales). A discussion of the further development of this
portion of the digestive tract, however, has been omitted from
the present paper.


The development of longitudinal folds
The epithelial tube of the transverse colon is of the same size as the ascending, and shows six well marked projections into the lumen, two of which are folds. In the upper part of the descending colon, two ridges and two folds are present. In the iliac colon the folds drop out and only ridges are found. When followed downward, the descending colon shows more and more ridges and when the sigmoid colon is reached there are as many as ten or twelve. Still more caudally the rectum shows folds which have taken the place of the ridges. In the lower part of the rectum, just above the rectal arnpulla, practically all the ridges have been replaced by folds, varying from ten to fourteen in number. The appearance obtained from cross sections, therefore, is somewhat similar to that found in the stomach of the same and slightly older embryos—the clefts in between the ridges corresponding to the gastric pits. The clefts, however, are broader and the cells of the epithelium lining them are more columnar in form than those of the gastric pits. Throughout all these portions of the large intestine the cells on the crests of the ridges differ from those between them. In the rectum the epithelium is distinctly one-layered. On the crests of its folds it presents a number of cells with clear protoplasm and basal nuclei. These presumably are developing goblet cells. In the colon of an embryo of 58 mm. the epithelial tube is found to be quite similar to that of the 55 mm. embryo just described. It is slightly smaller throughout than in the previous stage, which difference may in part be accounted for by the different kinds of preserving fluids used. In the cephalic end of the ascending colon the epithelial tube has now a diameter of 0.38 mm. and shows numerous ridges and folds as seen in figure 15. More caudally in the ascending colon the epithelium is not so irregular as near the eaecum. As seen in sections three folds and one ridge are present. Figure 16 shows a model of this portion of the intestine. It is to be noted that the tops of the longitudinal folds are irregular in form. The diameter of this region of the glit is about 0.36 mm., while the epithelium averages about 0.050 mm. in thickness.


In an embryo of 22.8 mm. one sees for the first time a change
* 1 In this and all remaining text figures certain histological details -“have been omitted.  
in the form of the epithelium. In the colic ampulla, which now
has a diameter of 0.20 mm., the epithelium shows three low
longitudinal ridges on its inner surface. These ridges also
extend for short distances into the colon and vermiforrn process.


It becomes necessary at this point to explain the manner in
which the terms ‘ridges’ and ‘folds’ have been used throughout the remainder of this article. The term ‘ridge’ has been
employed to designate a thickening of the epithelium which
projects into the lumen. It must have no corresponding indentation on its under surface into which mesenchyma would extend. By a ‘fold’ is meant a projection with an indented basal
surface, into which the underlying mesenchyma protrudes. This
distinction is desirable, as its usage makes it possible to explain
in few words the shape of the basal surface of the epithelium
along with that of its free surface.
192 FRANKLIN PARADISE JOHNSON


The epithelium in the embryo under consideration (22.8 mm.)
Fig. 11 Cross section of the transverse colon of a human embryo of 50 mm. X 60.
varies in thickness in different regions. In the colic ampulla
and vermiform process it is 0.056 mm. thick and shows three
to four rows of nuclei. In the remainder of the colon down to
the rectal ampulla, it is only 0.034 mm. in thickness and shows
but two to three rows of nuclei. At no place are the boundaries between the cells distinct, but the free and basal surfaces
are well marked.


In an embryo of 30 mm. the whole of the vermiform process
and the valve of the colon lie in the coelom of the umbilical
cord. An examination of the interior of the colon in this region
shows the beginnings of two to three epithelial ridges. These
Vary in height, the epithelium being 0.070 mm. thick, measured


‘through the summit of the largest ridge, while in the depressions


between them, it is only about 0.028 mm. thick. Three or four
rows of nuclei can be made out. The remainder of the colon
has an average diameter of 0.15 mm. Throughout its great
length the epithelial tube is still cylindrical in shape, having a
wall 0.048 mm. in.thickness. Three or four rows of nuclei are
present.


At 37' mm. the whole of the vermiform process still lies in
the umbilical cord. The epithelial ridges are higher than in
the former stages. In the base of the vermiform process there
are four of these, in the middle only three; in the beginning of
the colon, three or four. The highest ridge measures about
0.10 mm. in height and has three or four rows of nuclei. Between
the ridges the epithelium is only 0.042 mm. thick and shows
but two or three nuclear layers. The remainder of the large
intestine gradually decreases in size when followed caudally.
The portion which is to become the ascending colon is 0.27 mm.
in diameter; the transverse 0.22 mm.; and the descending colon
0.18 mm. The epithelium is about 0.056 mm. thick in all these
portions. A few vacuoles, such as have been found in the epithelial walls of the stomach and oesophagus are present in the
colon of this embryo.


In an embryo of 42 mm. the ridges of the epithelium are in
part replaced by true longitudinal folds. In the Vermiform procDEVELOPMENT or THE LARGE INTESTINE 193


ess and ascending colon three to four of these are present; in the
Fig. 2 Cross section of the transverse colon of a human embryo of 58 mm. X 60.
transverse colon two to three; in the greater part of the descending colon three; while in the remainder of the descending colon five
to six more irregular ones. These folds vary in height from 0.014
to 0.028 mm. The epithelium is thicker on their crests than
between them. It presents an appearance which is largely in
accordance with a condition which Patzelt (’83) has found in
the large intestine of the cat embryo. He describes two types
of cells. In the corners of the star-shaped lumen the cells are
short and broad, and have basal nuclei which stain intensely
with haemotoxylin. The cells of the ‘second type are found on
the tops of the folds. They are longer, finely granular, and
somewhat denser. Their nuclei are long—oval or drop-shaped
and stain more intensely than those of the first type. The for~
mer groups of cells he states are the first anlagen of the Lieberkiilin glands; the latter of the villi. The epithelium of the large
intestine of the embryo under consideration (42 mm.) has been
described and pictured by Lewis (’11). The two types of cells
are found arranged in separate groups, but, however, are not
as distinct as those of the cat described by Patzelt.


In the ascending colon of an embryo of 50 mm., the epithelial
tube has a diameter of about 0.23 mm., and shows four distinct
longitudinal folds. These are, as shown in figure 12, rounded
on their tops, and are of different heights, the largest measuring
about 0.06 mm. In the piece of ascending colon sectioned for
study, which measures about 0.7 mm. in length, the epithelial
tube changes but little in shape, the four distinct longitudinal
folds running throughout. The epithelium, which has an aVer~
age thickness of 0.050 mm., is columnar, and, as seen in sections
ten microns thick, is apparently stratified, being composed of
two or perhaps three, layers of cells. The nuclei, which are
oval in shape, are all placed in a zone midway between the free
and basal surfaces of the epithelium, there being a clear zone
of protoplasm on either side. A definite cuticular border is
everywhere present on the free surface of the epithelium. Two
distinct types of cells are not visible. Outside of the epithelium
is a zone of loose mesenchyma which is bounded by a thin layer
194 FRANKLIN PARADISE JOHNSON


of myoblasts, the circular layer of the muscularis. This is in
The transverse colon of an embryo of 58 mm. shows six distinct folds, as seen in figure 2. A model of one half of the tube of this region is represented in figure 17. The diameter of the epithelial tube averages 0.38 mm. The descending colon (fig. 18) has a diameter of 0.34 mm., is more rounded in shape, being quite similar to the more cephalic part of the ascending colon. The crests of the folds and ridges are, however, not so angular.
turn bounded by a layer of mesenchyma and surrounding the
whole, except at its mesenteric attachment, a distinct serous
epithelium is seen.


In passing ab-orally from the ascending colon into the transverse colon, one of the four longitudinal folds just described
===First appearance of villi===
drops out, while a second becomes so much reduced in size that
it is scarcely recognizable as a fold (figs. 1 and 13). The two
remaining folds are distinct andabout 0.06 mm. in height. The
epithelial tube has a diameter of about 0.27 mm. The remaining features of this portion of the large intestine are similar to
those of the ascending colon.


First appearance of goblet cells
In the rectum the epithelial folds have increased in size and give to the lumen a very irregular form. As shown in figure 19, some of the folds run almost transversely. The presence of transverse folds have been noted in the lower portion of the rectum in a number of older embryos as well. Besides folds, here and there are present conical—shaped projections of the epithelium. These represent the first transitory villi of the large intestine.


In the iliac colon (50 mm. embryo), the epithelial tube as a
whole is flattened from side to side. Its greater diameter is
0.36 mm., its lesser 0.18 mm. A considerable change in the
condition of folds is evident. They are shallow, irregular, and
more numerous than in the ascending and transverse colons.
A model of a small portion of this region is shown in figure 14.
The distinction between epithelial ridges and folds is here apparent——only those protuberances, which have indented basal surfaces into which the mesenchyma extends, being considered as
true folds. Measured through the ridges the epithelium is in
places 0.084 mm. thick, while in the clefts between them, it is
only 0.028 mm. thick. The two types of cells described by
Lewis in the 42 mm. stage are distinct. A few cells on the
ridges have a protoplasm .which is clearer than others, and are
shaped somewhat like goblet cells. Because these cells in the
next few stages take on more and more the appearance of goblet
cells until their identity cannot be doubted, I believe them to
be goblet cells in a very early stage of differentiation. Voigt
(’99) was able to distinguish goblet cells first in the rectum of a
human embryo of 70 mm.


The ascending colon of an embryo of 55 mm. has a diameter’
In a number of places the folds seem to be fused together at their tops, shutting off small rounded spaces. These spaces I have determined from serial sections to be epithelial cysts. They are found in corresponding portions of the rectum of other embryos, but are confined to this region of the large intestine alone. A portion of one of these cysts is shown in figure 19 at ya. They are described in detail below.
of 0.45 mm. Ten to twelve longitudinal ridges are found, but
DEVELOPMENT or THE LARGE INTESTINE 195


distinct folds are absent. The ridges are irregular in form and
of varying size, the largest being about 0.10 mm. in height.
The two types of cells are distinct now in this region of the large
intestine, some of which are like those which Patzelt has described as drop-shaped. In many places large vacuoles similar
to those described above are found in the epithelium of the ridges.


The epithelial tube of the transverse colon is of the same size
At this point it seems advisable to make the following summary regarding the development of ridges and folds. In the beginning the epithelial tube is cylindrical in shape. The first changes that take place in its form are found in the rectum, where it shows a number of longitudinal ridges. These ridges are the forerunners of folds, for everywhere they later appear as if pushed in from behind by the underlying mesenchyma. Soon afterward ridges and folds are found in the descending colon, the direction of growth being from below upward. However, before these changes have extended into the transverse colon, similar changes are found to be occurring in the ascending colon near to the colic valve. The direction of growth here is opposite that in the descending colon, that is, ab-orally. The transverse colon is, therefore, the last portion of the large intestine to develop folds. Similarly, in a few of the subsequent stages, the transverse colon shows a slight retardation in the development of villi and glands as compared with the rectum, descending and ascending colons. However, this retardation is soon overcome by an increased rate in growth, and then conditions found in all parts of the large intestine are quite similar. As a matter of convenience and simplicity, the development of the transverse colon has been described most completely in the remainder of this article, and other portions of the large intestine are described, as far is possible, from a comparative point of View with respect to it.
as the ascending, and shows six well marked projections into
the lumen, two of which are folds. In the upper part of the
descending colon, two ridges and two folds are present. In the
iliac colon the folds drop out and only ridges are found. When




Fig. 11 Cross section of the transverse colon of a human embryo of 50 mm.
Fig. 3 Cross section of the transverse colon of a human embryo of 65 mm. X 60.
X 60.


followed downward, the descending colon shows more and more
The transverse colon of an embryo of 65 mm. differs considerably from that of the embryo just described. The epithelial tube is circular in section and measures 0.54 mm. in diameter. In transverse section (fig. 3) eighteen to twenty-three projections are seen extending into the lumen. VVl1en modelled these projections are seen to be longitudinal folds and villi as shown in figure 20. The villi are everywhere arranged in longitudinal ows, suggesting that the folds have become broken up into segments. The folds and villi measure from 0.08 to 0.11 mm. in height and are usually between 0.07 and 0.11 mm. in width at their bases. The epithelium on their tops is distinctly simple columnar in form, and is reduced to 0.019 mm. in thickness; between the folds it is 0.031 mm. thick.
ridges and when the sigmoid colon is reached there are as many
as ten or twelve. Still more caudally the rectum shows folds
which have taken the place of the ridges. In the lower part
of the rectum, just above the rectal arnpulla, practically all the
ridges have been replaced by folds, varying from ten to fourteen in number. The appearance obtained from cross sections,
therefore, is somewhat similar to that found in the stomach of
the same and slightly older en1bryos—the clefts in between the
ridges corresponding to the gastric pits. The clefts, however,
are broader and the cells of the epithelium lining them are more


1 In this and all remaining text figures certain histological details -“have been
omitted.
196 FRANKLIN PARADISE JOHNSON


columnar in form than those of the gastric pits. Throughout
Numerous villi are found in the ascending colon. A comparison of these with those villi in the lower part of the ileum shows that the two are quite similar in form and size. At a short distance from the colic valve, the epithelial walls of the ascending colon become pushed in by three large Inesenchymal folds, reducing the lumen to a narrow Y—shaped cleft. Here are found folds and villi resembling those shown in figure 20. The descending colon is smaller in diameter than the transverse, being only 0.45 mm. An examination of its inner surface (fig. 21), shows folds and villi, and what apparently are partially formed villi, about eight to nine rows in all. These are longer than those of the transverse colon, 0.17 to 0.22 mm., but of about the same width. In the sigmoid colon is found a condition comparable to that of the descending colon. However, goblet cells are far more numerous.
all these portions of the large intestine the cells on the crests
of the ridges differ from those between them. In the rectum
the epithelium is distinctly one-layered. On the crests of its
folds it presents a number of cells with clear protoplasm and
basal nuclei. These presumably are developing goblet cells.
In the colon of an embryo of 58 mm. the epithelial tube is
found to be quite similar to that of the 55 mm. embryo just
described. It is slightly smaller throughout than in the previous
stage, which difference may in part be accounted for by the
different kinds of preserving fluids used. In the cephalic end


===First appearance of intestinal glands===


Fig. 2 Cross section of the transverse colon of a human embryo of 58 mm.
The epithelial tube of the upper portion of the rectum (embryo of 65 mm.) is flattened from side to side, and measures 1.17 by 0.77 mm. in cross section. A very different appearance is presented from that of the transverse colon. The epithelial wall is bent into a number of folds which are closely packed together. Many of these measure as much as 0.27 and 0.36 mm. in height. The bottoms of the spaces between these projections are developing glands. Where they are cut obliquely or in cross section their basal ends are seen to be tubular in form and provided with small round lumina. '
X 60.


of the ascending colon the epithelial tube has now a diameter
of 0.38 mm. and shows numerous ridges and folds as seen in
figure 15. More caudally in the ascending colon the epithelium
is not so irregular as near the eaecum. As seen in sections three
folds and one ridge are present. Figure 16 shows a model of
this portion of the intestine. It is to be noted that the tops
of the longitudinal folds are irregular in form. The diameter
of this region of the glit is about 0.36 mm., while the epithelium
averages about 0.050 mm. in thickness.


The transverse colon of an embryo of 58 mm. shows six distinct folds, as seen in figure 2. A model of one half of the tube
Epithelial cysts are more numerous than in the preceding embryo. They represent glands and intervillous spaces which have become closed over at their tops. They show evidences of internal pressure by their bulbous appearance and by the flattening of the lining epithelium of the more superficially lying part of the cyst (fig. 11). In many respects these cysts are similar to those found in the vermiform process (compare fig. 11 with figs. 9 and 10) but differ from them by their more superficial position and in that they can rarely be considered to be entirely separated from the surface epithelium. Moreover, they have a different fate from those of the vermiform process. Instead of the epithelium entirely degenerating, the cyst collapsing, and finally being absorbed, the cysts of the rectum open up with the intestinal lumen and become glands again, at least this interpretation seems justifiable, since the cysts gradually disappear Without showing such degenerative processes as are easily recognizable in those of the vermiform process.
of this region is represented in figure 17. The diameter of the
DEVELOPMENT OF THE LARGE INTESTINE 197


epithelial tube averages 0.38 mm. The descending colon (fig.
18) has a diameter of 0.34 mm., is more rounded in shape, being
quite similar to the more cephalic part of the ascending colon.
The crests of the folds and ridges are, however, not so angular.


First appearance of villi
The condition found in the transverse colon of an embryo of 70 mm. is not much in advance of the same portion of the large intestine at 65 mm. Its epithelial tube has a diameter of 0.54 mm. The lumen is relatively large and the villi project into it 0.09 to 0.13 mm. The cells forming the epithelium are tall columnar, 0.025 in height, and contain at their basal ends, elongated nuclei. The protoplasm, which stains decidedly yellow with orange—G, appears to be mucous in character. Here and there swollen goblet cells are seen. A small portion of the sigmoid colon presents an appearance similar to that described in the rectum at 65 mm. It measures 0.54 mm. by 0.72 mm., and contains folds and villi 0.23 to 0.27 mm. in height. Epithelial glands and cysts are found in large numbers. In the rectum the same conditions are presented, although the epithelial tube is larger and the villi taller (0.25 to 0.32 mm.). The latter seem, however, to be so fused together that they appear in many places as irregular running folds. Goblet cells are everywhere numerous.


In the rectum the epithelial folds have increased in size and
give to the lumen a very irregular form. As shown in figure
19, some of the folds run almost transversely. The presence
of transverse folds have been noted in the lower portion of the
rectum in a number of older embryos as well. Besides folds, here
and there are present conical—shaped projections of the epithelium.
These represent the first transitory villi of the large intestine.


In a number of places the folds seem to be fused together
In-a well preserved transverse colon of an embryo of 73 mm. the epithelial tube measures 0.58 mm. in diameter. The villi and folds, some of which are now 0.22 to 0.23 mm. high, decrease to a marked extent the size of the lumen. In width the villi show a slight increase, being 0.09 to 0.18 mm. through at their bases. The tops of the villi are in many places so closely approximated that it is quite impossible from cross sections of this stage alone to determine whether an actual fusion has or has not taken place. Because of this condition, which I believe to have been brought about by a strong contraction of the muscularis, an attempt to model these villi accurately proved fruitless. From the conditions found in the large intestine, of other embryos of about the same age, however, it would not seem probable that such a thing as an actual fusion had taken place. The epithelium on the tops of the projections is distinctly one-layered and 0.025 to 0.028 mm. thick, while between them it appears two—layered, and is almost twice as thick, 0.042 to 0.052. Only the portions of the epithelium in between villi are provided with distinct basement membranes.
at their tops, shutting off small rounded spaces. These spaces
I have determined from serial sections to be epithelial cysts.
They are found in corresponding portions of the rectum of other
embryos, but are confined to this region of the large intestine
alone. A portion of one of these cysts is shown in figure 19
at ya. They are described in detail below.


At this point it seems advisable to make the following summary regarding the development of ridges and folds. In the
beginning the epithelial tube is cylindrical in shape. The first
changes that take place in its form are found in the rectum,
where it shows a number of longitudinal ridges. These ridges
are the forerunners of folds, for everywhere they later appear
as if pushed in from behind by the underlying mesenchyma.
Soon afterward ridges and folds are found in the descending
colon, the direction of growth being from below upward. However, before these changes have extended into the transverse
colon, similar changes are found to be occurring in the ascending colon near to the colic valve. The direction of growth here
is opposite that in the descending colon, that is, ab-orally. The
transverse colon is, therefore, the last portion of the large intestine to develop folds. Similarly, in a few of the subsequent
stages, the transverse colon shows a slight retardation in the
198 FRANKLIN PARADISE JOHNSON


development of villi and glands as compared with the rectum,
descending and ascending colons. However, this retardation is
soon overcome by an increased rate in growth, and then conditions found in all parts of the large intestine are quite similar.
As a matter of convenience and simplicity, the development of
the transverse colon has been described most completely in the
remainder of this article, and other portions of the large intestine are described, as far  is possible, from a comparative
point of View with respect to it.


Fig. 4 Cross section of the transverse colon of a human embryo of 88 mm. X 60.


Fig. 3 Cross section of the transverse colon of a human embryo of 65 mm.
In the descending colon practically the same conditions are repeated, with the exception that a few more villi are present.
X 60.


The transverse colon of an embryo of 65 mm. differs considerably from that of the embryo just described. The epithelial tube is circular in section and measures 0.54 mm. in diameter.
In the transverse colon at 75 mm., even though considerable shrinkage is present, the villi are seen distinctly separated from one another. Other portions of the large intestine from the two last—mentioned embryos were not obtained.
In transverse section (fig. 3) eighteen to twenty-three projections are seen extending into the lumen. VVl1en modelled these
projections are seen to be longitudinal folds and villi as shown
in figure 20. The villi are everywhere arranged in longitudinal
DEVELOPMENT OF THE LARGE INTESTINE


rows, suggesting that the folds have become broken up into
In the transverse colon of an embryo of 88 mm. (fig. 4), are found numerous villi, which are arranged so that they form longitudinal rows. The epithelium on the tops and sides of the villi is similar to that of the preceding stages, being simple columnar in form and containing goblet cells. Between the villi the cells are tall cylindrical and conical in shape, contain oval nuclei which seem to be closely crowded together, and stain intensively. These groups of cells form small knob-like projections and are the beginnings of the intestinal glands.
segments. The folds and villi measure from 0.08 to 0.11 mm.
in height and are usually between 0.07 and 0.11 mm. in width
at their bases. The epithelium on their tops is distinctly simple columnar in form, and is reduced to 0.019 mm. in thickness;
between the folds it is 0.031 mm. thick.


Numerous villi are found in the ascending colon. A comparison of these with those villi in the lower part of the ileum shows
that the two are quite similar in form and size. At a short distance from the colic valve, the epithelial walls of the ascending
colon become pushed in by three large Inesenchymal folds, reducing the lumen to a narrow Y—shaped cleft. Here are found
folds and villi resembling those shown in figure 20. The descending colon is smaller in diameter than the transverse, being
only 0.45 mm. An examination of its inner surface (fig. 21),
shows folds and villi, and what apparently are partially formed
villi, about eight to nine rows in all. These are longer than
those of the transverse colon, 0.17 to 0.22 mm., but of about
the same width. In the sigmoid colon is found a condition
comparable to that of the descending colon. However, goblet
cells are far more numerous.


First appearance of intestmal glands
In the ascending, descending, and sigmoid eolons, as seen from transverse and longitudinal sections, both villi and the beginnings of glands are distinguishable. The villi graduall_v increase in length as the large intestine is followed caudally; thus in the ascending colon they are about 0.14 to 0.16 min. in height; in the transverse, 0.18 to 0.20 min.; in the descending colon, 0.22 to 0.25 mm.; in the sigmoid, 0.27 to 0.32 mm.; while in the rectum, 0.27 to 0.36 mm. In many places their apices are in close contact with each other, appearing as though fused. Likewise, the glands show a more advanced stage of growth as the large intestine is followed downward. In the ascending colon they are scarcely visible; in the rectum they are very distinct. Except for this more advanced stage of development, conditions in the rectum are not so strikingly different from those in the remainder of the colon as at a former period. The epithelial cysts, while not so numerous, have not entirely disappeared. Those few which remain are smaller and are confined to the lower part of the rectum.


The epithelial tube of the upper portion of the rectum (embryo
of 65 mm.) is flattened from side to side, and measures 1.17
by 0.77 mm. in cross section. A very different appearance
is presented from that of the transverse colon. The epithelial
wall is bent into a number of folds which are closely packed together. Many of these measure as much as 0.27 and 0.36 mm.
in height. The bottoms of the spaces between these projections
are developing glands. Where they are cut obliquely or in
cross section their basal ends are seen to be tubular in form and
provided with small round lumina. '


Epithelial cysts are more numerous than in the preceding
In an embryo of 99 mm. the transverse colon shows numerous villi arranged in rows, 20 to 25 in number. As seen in figure 23, few distinct folds are present, but these do not occur in any definite relation to the villi, that is, the rows of villi and the folds are not alternately placed around the Wall of the intestine. From this and from what I have seen in other embryos, it seems improbable that the new villi, which are now arising at a very rapid rate, are preceded by folds. hfore probably they develop after the manner of the villi in the small intestine, as separate growths between the villi already formed.
embryo. They represent glands and intervillous spaces which
have become closed over at their tops. They show evidences


mm AMERICAN JOURNAL or ANATOMY, voL. 14, NO. 2
200 FRAXKLIN PARADISE JoHi\'soN


of internal pressure by their bulbous appearance and by the
Numerous gland buds are also present in the specimen as shown in figure 23. “7 here the glands are cut in cross section, they show small but distinct lumina, surrounded by columnar cells of the mucous variety, many of which are goblet cells. On the tops and sides of the villi the epithelial cells are 0.022 to 0.028 mm. in height while in the glands they are 0.034 to 0.042 mm. Although shrunken from the underlying mesenehyma, the epithelial tube has increased to 1.03 mm. in diameter. The sigmoid colon has a diameter of 0.95 mm. and an epithelium which is similar in variety and of equal thickness to that just described.
flattening of the lining epithelium of the more superficially lying
part of the cyst (fig. 11). In many respects these cysts are
similar to those found in the vermiform process (compare fig.
11 with figs. 9 and 10) but differ from them by their more superficial position and in that they can rarely be considered to be
entirely separated from the surface epithelium. Moreover, they
have a different fate from those of the vermiform process. Instead of the epithelium entirely degenerating, the cyst collapsing, and finally being absorbed, the cysts of the rectum open up
with the intestinal lumen and become glands again, at least
this interpretation seems justifiable, since the cysts gradually
disappear Without showing such degenerative processes as are
easily recognizable in those of the vermiform process.


The condition found in the transverse colon of an embryo
of 70 mm. is not much in advance of the same portion of the
large intestine at 65 mm. Its epithelial tube has a diameter
of 0.54 mm. The lumen is relatively large and the villi project
into it 0.09 to 0.13 mm. The cells forming the epithelium are
tall columnar, 0.025 in height, and contain at their basal ends,
elongated nuclei. The protoplasm, which stains decidedly yellow with orange—G, appears to be mucous in character. Here
and there swollen goblet cells are seen. A small portion of the
sigmoid colon presents an appearance similar to that described
in the rectum at 65 mm. It measures 0.54 mm. by 0.72 mm.,
and contains folds and villi 0.23 to 0.27 mm. in height. Epithelial glands and cysts are found in large numbers. In the
rectum the same conditions are presented, although the epithelial tube is larger and the villi taller (0.25 to 0.32 mm.). The
latter seem, however, to be so fused together that they appear
in many places as irregular running folds. Goblet cells are
everywhere numerous.


In-a well preserved transverse colon of an embryo of 73 mm.
From this point on, measurements taken of the glands and villi can only be considered approximately accurate. This is due to the fact that there is no sharp line of demarcation between gland and villus, consequently one is unable to determine just where the gland begins and where the villus leaves ofl'. A similar difliculty was met with in the ease of the small intestine. It is, however, possible, with the aid of models for comparison,
the epithelial tube measures 0.58 mm. in diameter. The villi
and folds, some of which are now 0.22 to 0.23 mm. high, decrease
to a marked extent the size of the lumen. In width the villi
show a slight increase, being 0.09 to 0.18 mm. through at their
DEVELOPMENT on THE LARGE INTESTINE 20]


bases. The tops of the villi are in many places so closely approximated that it is quite impossible from cross sections of this stage
alone to determine whether an actual fusion has or has not taken
place. Because of this condition, which I believe to have been
brought about by a strong contraction of the muscularis, an
attempt to model these villi accurately proved fruitless. From
the conditions found in the large intestine, of other embryos
of about the same age, however, it would not seem probable
that such a thing as an actual fusion had taken place. The
epithelium on the tops of the projections is distinctly one-layered
and 0.025 to 0.028 mm. thick, while between them it appears


Fig. 5 Cross section of the transverse colon of a human embryo of 110 mm. X 60.


Fig. 4 Cross section of the transverse colon of a human embryo of 88 mm.
to judge the line of division approximately. In the following account of the growth of glands and villi, the figures given are the average of a number of measurements made from cross or longitudinal sections, or in some cases, from both. A more accurate method, which was employed whenever possible, was the direct measurement of these structures from the models themselves. In the transverse colon of the embryo under de~ scription (99 mm.), the glands may be regarded as about 0.07 mm. long and 0.056 mm. broad, while the villi as 0.27 mm. tall and 0.10 mm. broad. In the sigmoid colon the glands average 0.10 mm. and the villi 0.31 mm. in length.  
X 60.


tWo—layered, and is almost twice as thick, 0.042 to 0.052. Only
the portions of the epithelium in between villi are provided with
distinct basement membranes.


In the descending colon practically the same conditions are
In the transverse colon of an embryo of 110 mm. (fig. 5), the villi are long and narrow, and give to the colon the appearance of a small intestine of a slightly older embryo. Some of them measure as much as 0.36 to 0.45 mm. in length and average about 0.09 mm. in diameter at their bases. They are covered by a low columnar epithelium (cuboidal in places), which is rather poor in goblet cells. The glands are longer than those of the preceding stage, being about 0.13 to 0.16 mm. in length. The cells which line the glands are distinctly columnar, measuring from 0.022 to 0.028 mm. in height. By far the majority of these are goblet cells. Their nuclei are basally placed and closely crowded together, making this region of the gland very deeply stained.
repeated, with the exception that a few more villi are present.


In the transverse colon at 75 mm., even though considerable
shrinkage is present, the villi are seen distinctly separated from
one another. Other portions of the large intestine from the
two last—mentioned embryos were not obtained.


In the transverse colon of an embryo of 88 mm. (fig. 4), are
In the ascending colon, a similar picture is obtained. The villi are, however, somewhat shorter (0.27 to 0.36) mm. Noticeable again is the greater distribution of goblet cells in the glands than on the villi, and the difference in the height of the epithelium in the two regions- In the sigmoid colon and the rectum, the epithelial tube is larger and flattened from side to side. The villi and glands are quite similar as regards size, shape and structure to those in the ascending colon. No epithelial cysts were found in the piece of rectum examined, which was a portion taken rather high up.
found numerous villi, which are arranged so that they form
longitudinal rows. The epithelium on the tops and sides of the
villi is similar to that of the preceding stages, being simple columnar in form and containing goblet cells. Between the villi the
cells are tall cylindrical and conical in shape, contain oval nuclei
202 FRANKLIN PARADISE JOHNSON


which seem to be closely crowded together, and stain intensively. These groups of cells form small knob-like projections
and are the beginnings of the intestinal glands.


In the ascending, descending, and sigmoid eolons, as seen
In a Well preserved embryo of 120 mm., the transverse colon has a diameter of about 1.08 mm. in contrast to 1.26 mm. in the preceding embryo. The villi, which are closely packed together, are also shorter (0.18 to 0.27 mm.) than those of the former embryo, but the glands are of about the same length. This difference in size is probably due in part to the different preservating fluids used on the two embryos. The epithelium of both villi and glands is in excellent state of preservation and the goblet cells, which have taken the stain (orange—G) very strongly, stand out in marked contrast to the remaining cells. It is easily seen, therefore, that the goblet cells are more nurner— ous on the sides than on the tops of the villi and most numerous in the glands. In many glands these cells appear to be exclusively present. Although the glands are still only short knoblike projections (0.11 to 0.14 mm. in length and 0.09 mm. in width), some of them appear to be double. As will be subsequently described, this bifurcating of the glands is a very important factor in their multiplication.
from transverse and longitudinal sections, both villi and the
beginnings of glands are distinguishable. The villi graduall_v
increase in length as the large intestine is followed caudally;
thus in the ascending colon they are about 0.14 to 0.16 min. in
height; in the transverse, 0.18 to 0.20 min.; in the descending
colon, 0.22 to 0.25 mm.; in the sigmoid, 0.27 to 0.32 mm.; while
in the rectum, 0.27 to 0.36 mm. In many places their apices
are in close contact with each other, appearing as though fused.
Likewise, the glands show a more advanced stage of growth as
the large intestine is followed downward. In the ascending
colon they are scarcely visible; in the rectum they are very distinct. Except for this more advanced stage of development,
conditions in the rectum are not so strikingly different from
those in the remainder of the colon as at a former period. The
epithelial cysts, while not so numerous, have not entirely disappeared. Those few which remain are smaller and are confined
to the lower part of the rectum.


In an embryo of 99 mm. the transverse colon shows numerous
villi arranged in rows, 20 to 25 in number. As seen in figure
23, few distinct folds are present, but these do not occur in any
definite relation to the villi, that is, the rows of villi and the
folds are not alternately placed around the Wall of the intestine.
From this and from what I have seen in other embryos, it seems
improbable that the new villi, which are now arising at a very
rapid rate, are preceded by folds. hfore probably they develop
after the manner of the villi in the small intestine, as separate
growths between the villi already formed.


Numerous gland buds are also present in the specimen as
Conditions in the ascending colon, as regards villi and glands, are similar to those in the transverse. In the rectum the epithelial tube is again flattened laterally measuring 2.12 mm. by 0.69 mm. in cross section. The mucous membrane is thicker (0.32 to 0.36 mm.) than that of the transverse colon (0.27 to 0.32 mm.). Its villi are from 0.22 to 0.27 mm. in height and its glands about the same as those found in the transverse colon (0.13 to 0.16 mm.). Goblet cells are again very numerous. A few epithelial cysts were found in the extreme lower part of the rectum, but these were almost insignificant in size as compared to those of the former stages.
shown in figure 23. “7 here the glands are cut in cross section,
they show small but distinct lumina, surrounded by columnar
cells of the mucous variety, many of which are goblet cells. On
the tops and sides of the villi the epithelial cells are 0.022 to
0.028 mm. in height while in the glands they are 0.034 to 0.042
DEVELOPMENT or THE LARGE IN’I‘ES’1‘lNE 203


mm. Although shrunken from the underlying mesenehyma,
===Disappearance of villi===
the epithelial tube has increased to 1.03 mm. in diameter. The
sigmoid colon has a diameter of 0.95 mm. and an epithelium
which is similar in variety and of equal thickness to that just
described.


From this point on, measurements taken of the glands and
In an embryo of 140 mm. the transverse colon has a diameter of about 1.7 mm. and presents from thirty—siX to forty longitudinal rows of villi. It is apparent, therefore, that the villi are still increasing in numbers as the intestine is increasing in size. Since no distinct longitudinal folds can be found in either models or longitudinal sections, these additional villi must develop from the beginning as separate growths in the spaces between those villi already present. The form of the villi is shown in figure 24. Some of the tallest measure only 0.25 mm. in height. Disregarding the embryo of 120 mm., because of the undoubted shrinkage of all its parts, and referring to the 110 mm. stage, it is seen that the villi are shorter in the older embryo. Moreover, some of the villi are so short at 1-10 mm. that the term villus is scarcely applicable to them, but whether these are newly developed villi or dwindled—down old ones, I am unable to determine. Although the intestinal glands vary in length (0.13 to 0.18 mm.) they are on the whole slightly more advanced than before and many show signs of bilurcating. From the above observations it is evident that, as the glands are increasing in length, the villi are decreasing in height. In the subsequent stages of development, the villi become always lower and lower, so that it is now possible to say that the transitory villi reach their maximum height in embryos between 110 mm. and 140 mm., probably between 110 mm. and 120 mm.
villi can only be considered approximately accurate. This is
due to the fact that there is no sharp line of demarcation between
gland and villus, consequently one is unable to determine just
where the gland begins and where the villus leaves ofl'. A similar difliculty was met with in the ease of the small intestine.
It is, however, possible, with the aid of models for comparison,




Fig. 5 Cross section of the transverse colon of a human embryo of 110 mm.
In that portion of the ascending colon adjacent to the colic valve, shorter villi are found (0.14 to 0.18 mm. in height), which are also lower than those in the ileum (0.27 to 0.36 mm.). Higher up in the ascending colon the villi are of about the same size, While the glands are 0.13 to 0.18 mm. in length, and in the beginning of the ascending colon, a few enlarged glands, such as are present in the vermiform process, are found. As regards villi and glands, the descending colon is quite similar to the transverse colon. In the sigmoid colon the villi are longer (0.18 to 0.27 mm.); in the rectum (0.18 to 0.36 mm.). Everywhere, however, the glands remain about the same length as those of the transverse colon. The epithelium is also quite similar throughout the whole colon. It is high columnar in the glands, lower on the sides, and lowest on the apices of the villi. Goblet cells are extremely numerous everywhere, being more abundant in the glands than on the villi.
X 60.


to judge the line of division approximately. In the following
===Effects of distention caused by a storing up of meconium===
account of the growth of glands and villi, the figures given are
the average of a number of measurements made from cross or
longitudinal sections, or in some cases, from both. A more
accurate method, which was employed whenever possible, was
the direct measurement of these structures from the models
themselves. In the transverse colon of the embryo under de~
scription (99 mm.), the glands may be regarded as about 0.07
mm. long and 0.056 mm. broad, while the villi as 0.27 mm.
tall and 0.10 mm. broad. In the sigmoid colon the glands average 0.10 mm. and the villi 0.31 mm. in length.
204
I FRANKLIN PARADISE JOHNSON


In the transverse colon of an embryo of 110 mm. (fig. 5), the
A marked difference in the thickness of the mucosa is found between the transverse colon of an embryo of 187 mm. and that of the same portion of the intestine of an embryo of 190 mm. (Compare figs. 6 and 7). That of the former is 0.36 mm. in thickness, While that of the latter is only 0.16 to 0.20 mm., the first being about twice the thickness of the second. The question arises, how is this variation to be accounted for? It is to be noted that the portion of intestine of the 190 mm. embryo examined was filled with meconium, thereby extending its Walls and increasing the size of its lumen. The total diameter of its epithelial tube is 4.2 mm., in comparison to 2.3 mm. in the 187 mm. stage. These measurements show only that the epithelial tube is extended in the older stage, but they do not show that the circumference of one is greater in one than in the other, because in the younger stage the epithelial wall is thrown into three or four large folds. In order to determine accurately Whether the folds alone would compensate for so great a difference in diameter, enlarged camera drawings were made, and the length of the lines at the bases of the glands (the line at which the muscularis is just beginning to appear) was measured. The distended gut (190 mm. stage) measured 15.3 mm., while the contracted one only 11.3 mm., showing still a considerable unaccountable differenco. From What I have seen in this and other sections, in the small as WCll as in the large intestine, I have come to the conclusion that Wherever the embryonic intestine is greatly distended with rneconium, is often found to be the case in the older stages, the thickness of the mucosa becomes greatly reduced. In other words, where a considerable amount of meconium is found in the intestine, the thickness of its mucosa varies indirectly with the amount of distension.
villi are long and narrow, and give to the colon the appearance
of a small intestine of a slightly older embryo. Some of them
measure as much as 0.36 to 0.45 mm. in length and average
about 0.09 mm. in diameter at their bases. They are covered
by a low columnar epithelium (cuboidal in places), which is
rather poor in goblet cells. The glands are longer than those
of the preceding stage, being about 0.13 to 0.16 mm. in length.
The cells which line the glands are distinctly columnar, measuring from 0.022 to 0.028 mm. in height. By far the majority
of these are goblet cells. Their nuclei are basally placed and
closely crowded together, making this region of the gland very
deeply stained.


In the ascending colon, a similar picture is obtained. The
villi are, however, somewhat shorter (0.27 to 0.36) mm. Noticeable again is the greater distribution of goblet cells in the glands
than on the villi, and the difference in the height of the epithelium in the two regions- In the sigmoid colon and the rectum,
the epithelial tube is larger and flattened from side to side. The
villi and glands are quite similar as regards size, shape and structure to those in the ascending colon. No epithelial cysts were
found in the piece of rectum examined, which was a portion
taken rather high up.


In a Well preserved embryo of 120 mm., the transverse colon
Fig. 6 Longitudinal section of the transverse colon of a human embryo of 187 mm. X (50. Shows state of normal contraction (compare villi and glands with those of fig. 7).
has a diameter of about 1.08 mm. in contrast to 1.26 mm. in
the preceding embryo. The villi, which are closely packed
together, are also shorter (0.18 to 0.27 mm.) than those of the
former embryo, but the glands are of about the same length.
This difference in size is probably due in part to the different
preservating fluids used on the two embryos. The epithelium
of both villi and glands is in excellent state of preservation and
the goblet cells, which have taken the stain (orange—G) very
strongly, stand out in marked contrast to the remaining cells.
It is easily seen, therefore, that the goblet cells are more nurner—
ous on the sides than on the tops of the villi and most numerous
in the glands. In many glands these cells appear to be
exclusively present. Although the glands are still only short
DEVELOPMENT or THE LARGE INTESTINE 205


knoblike projections (0.11 to 0.14 mm. in length and 0.09
mm. in width), some of them appear to be double. As will be
subsequently described, this bifurcating of the glands is a very
important factor in their multiplication.


Conditions in the ascending colon, as regards villi and glands,
Fig. 7 Cross section of the transverse colon of a human embryo of 190 mm. X B0 (compare with fig. (3).
are similar to those in the transverse. In the rectum the epithelial tube is again flattened laterally measuring 2.12 mm. by
0.69 mm. in cross section. The mucous membrane is thicker
(0.32 to 0.36 mm.) than that of the transverse colon (0.27 to
0.32 mm.). Its villi are from 0.22 to 0.27 mm. in height and its
glands about the same as those found in the transverse colon
(0.13 to 0.16 mm.). Goblet cells are again very numerous.
A few epithelial cysts were found in the extreme lower part of
the rectum, but these were almost insignificant in size as compared to those of the former stages.


Disappeararncc of villi


In an embryo of 140 mm. the transverse colon has a diameter
Since the perimeters of the two colons under discussion were unequal in length, it is of interest to compare the number of glands present in them. This was done by counting the number of glands which were practically in contact with the developing muscularis mucosae. This method would not have given comparable results had not the thickness of the sections in both cases been the same (8 microns). In the distended intestine variations from 79 to 96 and an average of 86 were obtained; in the non-distended piece, a variation from 81 to 91 and an average of 85.2, showing that the number of glands is approximately the same. Whether the number of villi around the intestinal wall is the same in both of the intestines, is a harder problem to determine, owing to their greater size and irregularity in height, and to the fact that one is given no distinct basal line, as in the case of the glands, from which to measure. Such a problem could only be determined with any degree of accuracy by making a number of models of comparatively large areas. However, from cross sections alone, it is possible to make out that in the distended intestine the villi are further apart.
of about 1.7 mm. and presents from thirty—siX to forty longitudinal rows of villi. It is apparent, therefore, that the villi
are still increasing in numbers as the intestine is increasing in
size. Since no distinct longitudinal folds can be found in either
models or longitudinal sections, these additional villi must develop from the beginning as separate growths in the spaces
between those villi already present. The form of the villi is
shown in figure 24. Some of the tallest measure only 0.25 mm.
in height. Disregarding the embryo of 120 mm., because of
the undoubted shrinkage of all its parts, and referring to the
110 mm. stage, it is seen that the villi are shorter in the older
embryo. Moreover, some of the villi are so short at 1-10 mm.
that the term villus is scarcely applicable to them, but whether
these are newly developed villi or dwindled—down old ones, I
am unable to determine. Although the intestinal glands vary
in length (0.13 to 0.18 mm.) they are on the whole slightly more
advanced than before and many show signs of bilurcating. From
the above observations it is evident that, as the glands are in206 FRANKLIN PARADISE JOHNSON


creasing in length, the villi are decreasing in height. In the
In the spreading or stretching out of the mucosa, both the villi and glands become reduced in length. and broadened. The following measurements have been made to show this:
subsequent stages of development, the villi become always lower
<br>
and lower, so that it is now possible to say that the transitory
{{Johnson1913table3}}
villi reach their maximum height in embryos between 110 mm.
and 140 mm., probably between 110 mm. and 120 mm.


In that portion of the ascending colon adjacent to the colic
It must be noted that the villi had in many places practically disappeared.
valve, shorter villi are found (0.14 to 0.18 mm. in height), which
are also lower than those in the ileum (0.27 to 0.36 mm.). Higher
up in the ascending colon the villi are of about the same size,
While the glands are 0.13 to 0.18 mm. in length, and in the beginning of the ascending colon, a few enlarged glands, such as are
present in the vermiform process, are found. As regards villi
and glands, the descending colon is quite similar to the transverse colon. In the sigmoid colon the villi are longer (0.18 to
0.27 mm.); in the rectum (0.18 to 0.36 mm.). Everywhere,
however, the glands remain about the same length as those
of the transverse colon. The epithelium is also quite similar
throughout the whole colon. It is high columnar in the glands,
lower on the sides, and lowest on the apices of the villi. Goblet
cells are extremely numerous everywhere, being more abundant
in the glands than on the villi.


Eflccts of distention caused by a storing up of mecomuim
The outer layers of the intestine are also reduced in thickness by distension, a fact which is of common observance in the digestive tube of the adult. In the non-distendecl transverse colon the submucosa, the muscularis, and the serosa together measure about 0.24 mm., the distended one, 0.13 mm.


A marked difference in the thickness of the mucosa is found
between the transverse colon of an embryo of 187 mm. and that
of the same portion of the intestine of an embryo of 190 mm.
(Compare figs. 6 and 7). That of the former is 0.36 mm. in
thickness, While that of the latter is only 0.16 to 0.20 mm., the
first being about twice the thickness of the second. The question arises, how is this variation to be accounted for? It is
to be noted that the portion of intestine of the 190 mm. embryo
examined was filled with meconium, thereby extending its Walls
and increasing the size of its lumen. The total diameter of
its epithelial tube is 4.2 mm., in comparison to 2.3 mm. in the
187 mm. stage. These measurements show only that the epithelial tube is extended in the older stage, but they do not show
DEVELOPMENT OF THE LARGE INTESTINE 207


From the above given figures, the effects of distention, caused by a storing up of meconiuin in the large intestine may be enumerated as follows: (1) an increase in the diameter of the epithelial tube; (2) an increase in the actual surface on which the basal ends of the glands lie’; (3) a decrease in the thickness of the mucous membrane as a whole; (4) a decrease in the length of the glands and an increase in their width ; (5) a more marked decrease in the height of the villi and an increase in their width (6) a spreading apart of the glands and of the villi; and (7) a decrease in thickness in the outer coats of the intestine.


Fig. (3 Longitudinal section of the transverse colon of a human embryo of 187
mm. X (50. Shows state of normal contraction (compare villi and glands with
those of fig. 7).


Fig. 7 Cross section of the transverse colon of a human embryo of 190 mm.
The above results led to the question as to what eifect distention would have upon the intestine of an adult. The small intestine of a guinea—pig was experimentally distended with normal salt solution and fixed and hardened in that condition. Although the results of this and other experiments may be found in the following paper, it may be said here, that the results obtained are largely in accordance with those just described in the rneconium-filled intestine of the human embryo.
X B0 (compare with fig. (3).


that the circumference of one is greater in one than in the other,
because in the younger stage the epithelial wall is thrown into
three or four large folds. In order to determine accurately
Whether the folds alone would compensate for so great a difference in diameter, enlarged camera drawings were made, and
the length of the lines at the bases of the glands (the line at which
the muscularis is just beginning to appear) was measured. The
distended gut (190 mm. stage) measured 15.3 mm., while the
contracted one only 11.3 mm., showing still a considerable unaccountable differenco. From What I have seen in this and
other sections, in the small as WCll as in the large intestine, I
have come to the conclusion that Wherever the embryonic intestine is greatly distended with rneconium,  is often found to
be the case in the older stages, the thickness of the mucosa
208 FRANKLIN PARADISE JOHNSON


becomes greatl_y reduced. In other words, where a considerable
Because of the above described effects of marked distention of the large intestine, it has been considered necessary, for the sake of comparison, to select only non—distended portions of the colon for modelling. In the case of the embryo of 190 mm. the sigmoid colon was chosen, for while this region contains meconium, there is no distention. This is made evident by the presence of longitudinal or oblique folds of the mucous membrane, and by the following measurements as compared with those of the transverse colon of the same embryo: diameter of intestine 3.4 mm. ; thickness of mucous membrane 0.34 mm. ,' thickness of outer intestinal coats, 0.23 mm. Figure 22 shows the epithelium of this region of the intestine in surface view. The villi have dwindled down until they appear merely as irregular knobs which are joined together at their bases in the form of ridges. These ridges are of various lengths but all are of about the same thickness. They run in different directions and anastomose with one another, thus marking the surface of the epithelium up into an irregular network such as Langer (’87) has described in connection with the developing colic valve. The clefts in between the ridges are deep, and into them open the lumina of the intestinal glands. An examination of the basal surface of another model (not figured), from the same portion of the large intestine, shows numerous tubular glands, many of which are unbranched, but the branched type is not uncommon.
amount of meconium is found in the intestine, the thickness
of its mucosa varies indirectly with the amount of distension.


Since the perimeters of the two colons under discussion were
unequal in length, it is of interest to compare the number of
glands present in them. This was done by counting the number of glands which were practically in contact with the developing muscularis mucosae. This method would not have given
comparable results had not the thickness of the sections in both
cases been the same (8 microns). In the distended intestine
variations from 79 to 96 and an average of 86 were obtained;
in the non-distended piece, a variation from 81 to 91 and an
average of 85.2, showing that the number of glands is approximately the same. Whether the number of villi around the
intestinal wall is the same in both of the intestines, is a harder
problem to determine, owing to their greater size and irregularity in height, and to the fact that one is given no distinct
basal line, as in the case of the glands, from which to measure.
Such a problem could only be determined with any degree of
accuracy by making a number of models of comparatively large
areas. However, from cross sections alone, it is possible to
make out that in the distended intestine the villi are further
apart.


In the spreading or stretching out of the mucosa, both the
As stated before, the first beginnings of the intestinal glands appear as small knob-like processes which extend into the underlying mesenchyma. At the time they appear no muscularis Inucosae is present. In embryos of 99 mm., 110 mm., 140 mm., the muscularis mucosae is still not visible ; nevertheless, the intestinal glands all reach a certain depth, so that in a section, a line drawn parallel to the surface of the mucous membrane would practically touch the bottoms of all the glands. It is along this line, or rather, slightly below it, that the muscularis mucosae is becoming visible in an embryo of 187 mm. It is seen as a slight condensation of the mesenchyma forming a circular band of about 0.014 mm. in thickness. In it are observable, though not very distinctly, developing rnyoblasts. The band is slightly more distinct at 190 mm., and separates the connective tissue of the submucosa, which is condensed and well stained, from that of the tunica propria, which is loosely arranged and only faintly or not at all stained. At 187 and 190 mm. the basal ends of the glands can be seen resting upon this layer of muscle.
villi and glands become reduced in length. and broadened. The
following measurements have been made to show this:


HEIGHT or wnrru or , , .
===Further formation of glands===
“LLEST “Lu BASES 0,, VI,” LENGTH or Gun Ds xx mm or caL.s.1\Ds


‘Pfl'I7L. ’ITL’Il‘l,. mm. WNM.
As the glands are gradually increasing in number as the growth of the embryo proceeds, the question arises, how are new glands formed? Do they develop like new villi, by evaginations of the epithelium between those already formed, or are they developed after the manner which Patzelt has described, by a longitudinal splitting of those already present? In his discussion of this point Patzelt says:


Non-distended. . 0.18-0.27 0.07-0.09 0.22 0.05-0.09
:"Noch eriibrigt es mir, die Art und Weise anzugeben, wie sich die Lieberki'1hn’schen Driisen verniehren. Bei der Durchsicht dcr Praparate, hauptsaehlieh aus den alteren Stadien, findet man oft im Grunde etwas verbreiterte Driisen. In der Mitte des verbreiterten Grundes erhebt sich ein Epithelhoekerchen. Oft aueh ist dieses Hockerchen nicht mehr blos aus Epithelzellen gebildet, sondern gleicht im Durehsehnitte einem mit Epithcl iiberkleideten Zottchen, welehes in das Innere der Driise hineinragt. Es entspricht dein Durehsehnitte eines kleinen Faltchens, welches den Grund der Druse in zwei Theile spaltet. Dieses Faltchen waehst immer hoher und hoher. Die Druse hat endlich das Aussehen, als ob in einem geineinsanien Vorraum zwei Drusenschlauehe miindeten (Fig. 29 e). Wenn schliesslich die Hohe des Faltchens in gleieher Ebene mit der Innenfléiehe des Darmes steht, ist der Theilungsprocess vollendet, es sind aus einer Driise zwei geworden."
Distended. .. . . .. 0.00-0.09 0.14-0.18 0. 1]--~0. 14 0.09-0.14


 
He further believes that the upward growing connective tissue papilla continues its upward growth after it reaches the surface level and thus gives rise to a new villus.


It must be noted that the villi had in many places practically
In further support of I’atzelt’s view regarding gland multiplication may be mentioned that if new glands appeared as new outward growths from the epithelium, then one would expect to find always in any fetal intestine glands which extended for varying distances toward the muscularis mucosae. However, such an appearance is never found. The basal ends of the glands, as seen in figures 5, 6, 7, 8, 24 and 25, all extend down to one general level, no intermediate lengths being present. The branched types of glands are always present, some with two, some with three, and some with even four divisions. The amount of bifurcation also varies as Patzelt has figured. As in all problems of growing structures, it is indeed difficult to say precisely what changes are taking place, but I believe it safe to say that in this case that additional glands are developed by a longitudinal splitting of those already present.
disappeared.


The outer layers of the intestine are also reduced in thickness
by distension, a fact which is of common observance in the
digestive tube of the adult. In the non-distendecl transverse
DEVELOPMENT on THE LARGE INTESTINE 209


colon the submucosa, the muscularis, and the serosa together
In the transverse colon of an embryo of 200 mm. practically the same conditions as those described for the sigmoid colon of the 190 mm. stage are encountered. The mucous membrane, although not thrown up into folds, does not appear stretched out. The villi are of various sizes, the tallest being from 0.14 to 0.18 mm. high. The intestinal glands measure from 0.18 to 0.22 mm. in length. Other measurements taken are as follows:
measure about 0.24 mm., the distended one, 0.13 mm.


From the above given figures, the effects of distention, caused
Diameter of epithelial tube 3.5 mm.  
by a storing up of meconiuin in the large intestine may be enumerated as follows: (1) an increase in the diameter of the epithelial tube; (2) an increase in the actual surface on which the
basal ends of the glands lie’; (3) a decrease in the thickness of
the mucous membrane as a whole; (4) a decrease in the length
of the glands and an increase in their width ; (5) a more marked
decrease in the height of the villi and an increase in their width
(6) a spreading apart of the glands and of the villi; and (7) a
decrease in thickness in the outer coats of the intestine.


The above results led to the question as to what eifect distention would have upon the intestine of an adult. The small
Perimeter, measured at bases of glands 11.1 mm.  
intestine of a guinea—pig was experimentally distended with
normal salt solution and fixed and hardened in that condition.
Although the results of this and other experiments may be found
in the following paper, it may be said here, that the results
obtained are largely in accordance with those just described in
the rneconium-filled intestine of the human embryo.


Because of the above described effects of marked distention
Thickness of mucosa 0.40 mm.  
of the large intestine, it has been considered necessary, for the
sake of comparison, to select only non—distended portions of the
colon for modelling. In the case of the embryo of 190 mm.
the sigmoid colon was chosen, for while this region contains
meconium, there is no distention. This is made evident by the
presence of longitudinal or oblique folds of the mucous membrane, and by the following measurements as compared with
those of the transverse colon of the same embryo: diameter of
intestine 3.4 mm. ; thickness of mucous membrane 0.34 mm. ,'
thickness of outer intestinal coats, 0.23 mm. Figure 22 shows
the epithelium of this region of the intestine in surface view.
The villi have dwindled down until they appear merely as irregular knobs which are joined together at their bases in the form
of ridges. These ridges are of various lengths but all are of
about the same thickness. They run in different directions and
anastomose with one another, thus marking the surface of the
210 FRANKLIN PARADISE JOHNSON


epithelium up into an irregular network such as Langer (’87)
Thickness of outer layers  .027 mm.
has described in connection with the developing colic valve.
The clefts in between the ridges are deep, and into them open
the lumina of the intestinal glands. An examination of the
basal surface of another model (not figured), from the same portion of the large intestine, shows numerous tubular glands, many
of which are unbranched, but the branched type is not uncommon.


As stated before, the first beginnings of the intestinal glands
Number of glands touching muscularis mucosae 75.0  
appear as small knob-like processes which extend into the underlying mesenchyma. At the time they appear no muscularis
Inucosae is present. In embryos of 99 mm., 110 mm., 140 mm.,
the muscularis mucosae is still not visible ; nevertheless, the
intestinal glands all reach a certain depth, so that in a section,
a line drawn parallel to the surface of the mucous membrane
would practically touch the bottoms of all the glands. It is
along this line, or rather, slightly below it, that the muscularis
mucosae is becoming visible in an embryo of 187 mm. It is
seen as a slight condensation of the mesenchyma forming a circular band of about 0.014 mm. in thickness. In it are observable, though not very distinctly, developing rnyoblasts. The
band is slightly more distinct at 190 mm., and separates the
connective tissue of the submucosa, which is condensed and
well stained, from that of the tunica propria, which is loosely
arranged and only faintly or not at all stained. At 187 and
190 mm. the basal ends of the glands can be seen resting upon
this layer of muscle.


Fu-rlher formation. of glands
Number of glands per running millimeter 6.7


As the glands are gradually increasing in number as the growth
In the iliac colon of the same embryo, a slight distention is present as is indicated by the thickness of both the mucosa (0.32 mm.) and the outer layers (0.18 mm.). Although the preservation of the embryo is poor, enough can be made out from it to see that both villi and glands are shorter and broader than in the transverse colon.
of the embryo proceeds, the question arises, how are new glands
formed? Do they develop like new villi, by evaginations of
the epithelium between those already formed, or are they developed after the manner which Patzelt has described, by a longitudinal splitting of those already present? In his discussion of
this point Patzelt says:
DEVELOPMENT or THE LARGE INTESTINE 211


Noch eriibrigt es mir, die Art und VVeise anzugeben, wie sich die
Lieberki'1hn’schen Driisen verniehren. Bei der Durchsicht dcr Praparate, hauptsaehlieh aus den alteren Stadien, findet man oft im Grunde
etwas verbreiterte Driisen. In der Mitte des verbreiterten Grundes
erhebt sich ein Epithelhoekerchen. Oft aueh ist dieses Hockerchen
nicht mehr blos aus Epithelzellen gebildet, sondern gleicht im Durehsehnitte einem mit Epithcl iiberkleideten Zottchen, welehes in das
Innere der Driise hineinragt. Es entspricht dein Durehsehnitte eines
kleinen Faltchens, welches den Grund der Druse in zwei Theile spaltet.
Dieses Faltchen waehst immer hoher und hoher. Die Druse hat
endlich das Aussehen, als ob in einem geineinsanien Vorraum zwei Drusenschlauehe miindeten (Fig. 29 e). VVenn schliesslich die Hohe des
Faltchens in gleieher Ebene mit der Innenfléiehe des Darmes steht, ist
der Theilungsprocess vollendet, es sind aus einer Driise zwei geworden.


He further believes that the upward growing connective tissue
In an embryo of 240 mm. the transverse colon shows some distention, but not so much as was seen in this portion of the large intestine at 190 mm. This is made evident by comparing the thicknesses of the mucosa and the outer coats. As seen in a model (not figured), made at double the magnification of the former model, the mucous membrane presents on its lumen surface a number of large irregular anastomesing folds. Between the folds are clefts, which in some places appear to be the glands themselves; in other places they are merely crypts into which the glands open. The glands are, for the greater part, of the simple tubular type, but some show bifurcations into two or three portions. The epithelium, which varies in thickness from 0.020 to 0.034 mm., is made up of the typical simple columnar cells found in the adult intestine, and contains large numbers of goblet cells. The following list of measurements is given for comparison with the other stages:
papilla continues its upward growth after it reaches the surface
level and thus gives rise to a new villus.


In further support of I’atzelt’s view regarding gland multiplication may be mentioned that if new glands appeared as
Total diameter of epithelial tube 4.6 mm.  
new outward growths from the epithelium, then one would
expect to find always in any fetal intestine glands which extended
for varying distances toward the muscularis mucosae. However, such an appearance is never found. The basal ends of
the glands, as seen in figures 5, 6, 7, 8, 24 and 25, all extend
down to one general level, no intermediate lengths being present.
The branched types of glands are always present, some with
two, some with three, and some with even four divisions. The
amount of bifurcation also varies as Patzelt has figured. As
in all problems of growing structures, it is indeed difficult to
say precisely what changes are taking place, but I believe it
safe to say that in this case that additional glands are developed
by a longitudinal splitting of those already present.


In the transverse colon of an embryo of 200 mm. practically
Perimeter, measured at the bases of the glands 14.8 mm.  
the same conditions as those described for the sigmoid colon of
the 190 mm. stage are encountered. The mucous membrane,
although not thrown up into folds, does not appear stretched
out. The villi are of various sizes, the tallest being from 0.14
to 0.18 mm. high. The intestinal glands measure from 0.18 to
0.22 mm. in length. Other measurements taken are as follows:


rum AMERICAN JOURNAL on ANATOMY, von. 14, NO. 2
Thickness of mucosa  0.36 mm.  
212 FRANKLIN PARADISE JOHNSON


Diameter of epithelial tube . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 3.5 mm.
Thickness of outer coats 0.22 mm.  
Perimeter, measured at bases of glands. . . . . . . . . . . . . . . . . . . . . . .11.1 mm.
Thickness of mucosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . _ _ _ , , . _0.40 mm.
Thickness of outer layers . . . . . . . i . . . . . . . . . . . . . . . . . . . . . . . . . . .027 mm,
Number of glands touching muscularis mucosae . i . . . . . . . . . . . .75.0
Number of glands per running millimeter . . . . . . . . . . . . . . . . . . . . . .6.7


In the iliac colon of the same embryo, a slight distention is
Number of glands touching muscularis mucosae 1140
present as is indicated by the thickness of both the mucosa
(0.32 mm.) and the outer layers (0.18 mm.). Although the
preservation of the embryo is poor, enough can be made out
from it to see that both villi and glands are shorter and broader
than in the transverse colon.


In an embryo of 240 mm. the transverse colon shows some
Number of glands per running millimeter  7.7
distention, but not so much as was seen in this portion of the
large intestine at 190 mm. This is made evident by comparing the thicknesses of the mucosa and the outer coats. As seen
in a model (not figured), made at double the magnification of
the former model, the mucous membrane presents on its lumen
surface a number of large irregular anastomesing folds. Between the folds are clefts, which in some places appear to be
the glands themselves; in other places they are merely crypts
into which the glands open. The glands are, for the greater
part, of the simple tubular type, but some show bifurcations
into two or three portions. The epithelium, which varies in
thickness from 0.020 to 0.034 mm., is made up of the typical
simple columnar cells found in the adult intestine, and contains
large numbers of goblet cells. The following list of measurements is given for comparison with the other stages:


Total diameter of epithelial tube. . . . ..................... 4.6 mm.
Perimeter, measured at the bases of the glands . . . . . . . . . . . . . .. 14.8 mm.
Thickness of mucosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.36 mm.
Thickness of outer coats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.22 mm.
Number of glands touching muscularis mucosae . . . . i . . . . . . . . .1140
Number of glands per running millimeter  . . . . . . . . . . . . . . . . . 7.7


In an embryo of 320 mm. a piece of transverse colon which
In an embryo of 320 mm. a piece of transverse colon which was greatly distended with meconium was examined. The large folds of the mucosa have all disappeared and the intestinal wall as a whole is considerably thinned out. Owing to poor preservation, however, it was not possible to determine the presence of villi and folds. Measurements made are as follows:
was greatly distended with meconium was examined. The large
folds of the mucosa have all disappeared and the intestinal wall
DEVELOPMENT or THE LARGE INTESTINE 213


as a whole is considerably thinned out. Owing to poor preservation, however, it was not possible to determine the presence
Total diameter of epithelial tube  5.5 X 14.5 mm.
of villi and folds. Measurements made are as follows:


Total diameter of epithelial tube . . . . . . . . . . . . . . . . . . . . . . .5.5 X 14.5 mm.
Perimeter, measured as before 34.7 mm.


Perimeter, measured as before . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34.7 mm.
Thickness of mucosa  0.16 mm.


Thickness of mucosa . . . . . . . . . . . . . . . . . . . . ‘ i . . . . . _ ‘ . . . . . . . . . . . . 0.16 mm.
Thickness of outer coats  0.20 mm.


Thickness of outer coats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0.20 mm.
NuIr1l)er of glands  269.0


NuIr1l)er of glands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269.0
Number of glands per millimeter  47.7


Number of glands per millimeter _ , . . . . . . . . . . . , . . . . . . . . . _ . . . . . 4 .7.7
In a fetus of about seven months (premature birth) the ascending colon seems to be almost entirely devoid of villi and the before-described folds. Although not modelled, it is plain to see that the surface epithelium is for the most part, though not entirely, level. At more or less regular intervals, it dips down into the cylindrical intestinal glands. Measurements:


In a fetus of about seven months (premature birth) the ascending colon seems to be almost entirely devoid of villi and the
Total diameter of epithelial 3.7 mm.  
before-described folds. Although not modelled, it is plain to
see that the surface epithelium is for the most part, though not
entirely, level. At more or less regular intervals, it dips down
into the cylindrical intestinal glands. Measurements:


Total diameter of epithelial  3.7 mm.
Perimeter 8.5 mm.
Perimeter . . . . . . . . . . . . . . . . . . . . . . . i . . . . . . i . . . . . . . . . . . . . . . . . . . . 18.5 mm.


Thickness of mucosa . . . . . . . . . . . . . . . . _ . . . . . . . . . . , . . . . . . . . , . . 0.27 mm.
Thickness of mucosa 0.27 mm.


Thickness of outer coats . . . . . . . . . . . . . . _ . , . . . . _ . . . . . . . i . . . . . 0.54 mm.
Thickness of outer coats 0.54 mm.


Number of glands . . . . . . . . . . . . . . . . . . . . . _ _ . . . . . . _ . . . . . . . . . _ . _162.0
Number of glands 162.0


Number of glands per millimeter . . . . . . . . . . . . . . . . . . . . . . . . . . . _ 8.’?
Number of glands per millimeter 8.’?


Sections of the sigmoid colon show a similar condition as
Sections of the sigmoid colon show a similar condition as regards glands. They are of an equal length and similarly distributed.
regards glands. They are of an equal length and similarly distributed.




Fig. 8 Cross section of the mucosa of the transverse colon of a human embryo
at birth. X 60.


Ina fully developed fetus at birth (fig. 8), a condition is reached
Fig. 8 Cross section of the mucosa of the transverse colon of a human embryo at birth. X 60.
in which the villi have entirely disappeared. A model of a portion of the epithelium of the transverse colon is shown in figure
25. As seen from the model, only glands are present, the openings of which appear irregular when viewed from the lumen
214 FRANKLIN PARADISE JOHNSON


side. For the most part the mouths of the glands open singly
to the surface, but in one region of the model, three can be seen
opening together in a slightly depressed region of the surface
epithelium. The glands are still of the simple and bifurcated
types, the bifurcated cries representing different stages in the
process of splitting. The epithelium, which is similar to that
in the adult, is 0.017 mm. in thickness at the surface, while in
the glands it measures 0.28 mm. Goblet cells are still numerous. Measurements made from cross sections of the transverse
colon at birth are as follows:


Diameter of epithelial tube . . . . . . . _ . . . . . . . . . . . . . . . . . . . , , . . . 5.5 mm.


Perimeter . . . , _ , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . 39.0 mm.
In a fully developed fetus at birth (fig. 8), a condition is reached in which the villi have entirely disappeared. A model of a portion of the epithelium of the transverse colon is shown in figure 25. As seen from the model, only glands are present, the openings of which appear irregular when viewed from the lumen side. For the most part the mouths of the glands open singly to the surface, but in one region of the model, three can be seen opening together in a slightly depressed region of the surface epithelium. The glands are still of the simple and bifurcated types, the bifurcated cries representing different stages in the process of splitting. The epithelium, which is similar to that in the adult, is 0.017 mm. in thickness at the surface, while in the glands it measures 0.28 mm. Goblet cells are still numerous. Measurements made from cross sections of the transverse colon at birth are as follows:


’l‘hic-liness of mucosa . . . . . . . . . . . . . , . . . , . . . . . . . . . . . . . . . , . . . . . 0.25 mm.
Diameter of epithelial tube  5.5 mm.


Thickness of outer coats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . _ 0.27-0.72 mm.
Perimeter 39.0 mm.


Number of glands . . . . _ . , . . . . . . . . . . . . . . . . . . . . . . . . . . . . . , . . . .3840
’l‘hic-liness of mucosa  0.25 mm.


Number of glands per millimeter . . . . . . . . . . . , . . . . . . . . . . . . . . . 9.8
Thickness of outer coats  0.27-0.72 mm.
Summary


To the foregoing observations the following summary may be
Number of glands  3840
added. As has been pointed out before, the cylindrical tube of
epithelium of the early stages develops longitudinal thickenings
or ridges. In an embryo of 58 mm. these are becoming partially transformed into low longitudinal folds. In embryos of
65 mm. these folds apparently segment, and in embryos of 88
to 99 mm. true villi are present. We have, therefore, longitudinal folds apparently subdivided to form villi. This view
concerning the formation of the villi in the small intestine has
been presented by Berry (’00) and confirmed by Forssner (’07).
In opposition to this, the view that the villi arise as separate
growths of the epithelium, not preceded by folds, has been
maintained by Koelliker (’61 and ’79), Barth C68), and Brand
(’77). Voigt C09) believed that the surface epithelium was cut
up into a number of elevations by a net Work of fissures and
furrows, and that these elevations grew into villi. In a study
of the development of the Whole of the human small intestine
the present author (’10) Wrote:
DEVELOPMENT on THE LARGE INTESTINE 215


In briefly summarizing the development of villi, it may be said that
Number of glands per millimeter  9.8
the general tendency throughout the whole of the small intestine is
for villi to develop as separate invaginations of the epithelium. Owing
however, to the occurrence of transitory structures (vacuoles, diverticula, and folds) their development is manifested differently in different parts of the intestine.


Although in the large intestine formation of villi is preceded
===Summary===
by distinct longitudinal folds, it does not seem probable to me,
after a study of my models, that there is a mechanical segmentation of the longitudinal folds. It must be remembered that
the epithelial tube is ever growing by an increase in the number
of its cells, and by the enlargement and duplication of its parts.
Because of this active growth one would expect, therefore, villi
to form by an active direct process, rather than by an indirect
one. It seems more probable to me, that small knob—like elevations are developed along the tops of the folds, and that these
knobs form into villi. If such were the case, the picture presented would always be one which would appear like a segmen—
tation of folds. As the villi grew taller and taller, the segmenting fissures would appear to be sinking in deeper and deeper.
It is important in this connection to note that the original folds
are considerably smaller than the villi, a fact which is in favor
of the view just proposed. Regarding the further development
of villi, it may be said with certainty, that they arise separately
in between those already present.


The earliest glands develop as small knob—like growths of the
To the foregoing observations the following summary may be added. As has been pointed out before, the cylindrical tube of epithelium of the early stages develops longitudinal thickenings or ridges. In an embryo of 58 mm. these are becoming partially transformed into low longitudinal folds. In embryos of 65 mm. these folds apparently segment, and in embryos of 88 to 99 mm. true villi are present. We have, therefore, longitudinal folds apparently subdivided to form villi. This view concerning the formation of the villi in the small intestine has been presented by Berry (’00) and confirmed by Forssner (’07). In opposition to this, the view that the villi arise as separate growths of the epithelium, not preceded by folds, has been maintained by Koelliker (’61 and ’79), Barth C68), and Brand (’77). Voigt C09) believed that the surface epithelium was cut up into a number of elevations by a net Work of fissures and furrows, and that these elevations grew into villi. In a study of the development of the Whole of the human small intestine the present author (’10) Wrote:
epithelium into the mesenchyma. As has been pointed out
before, the additional glands are probably formed by a longitudinal splitting of those already present.


The villi reach their maximum height in embryos of 110 mm.
In briefly summarizing the development of villi, it may be said that the general tendency throughout the whole of the small intestine is for villi to develop as separate invaginations of the epithelium. Owing however, to the occurrence of transitory structures (vacuoles, diverticula, and folds) their development is manifested differently in different parts of the intestine.
to 140 mm. in length. From this stage on they gradually become smaller and smaller. A fusion of adjacent villi together
at their bases, which gradually extends towards their apices and
lengthens the intestinal glands, has been described by Koelliker
(’61) and Schultze (’99) as the manner in which they disappear.
Brand (’77) describes the connective tissue about the glands
as the active factor in their disappearance. He believes that
216 FRANKLIN PARADISE JOHNSON


the connective tissue gradually grows higher and higher, and
in so doing, moulds the epithelium of the villi into that of the
glands. Schirman (’98) describes the disappearance of the villi
of the large intestine of the guinea-pig in an entirely different
manner as follows:


Die cmbryonalen Zotten des Dickdarms bestehen beim l\/leerschweinchen zu vier Funfteln ihrcr Liinge einzig aus Epithelzellen, nur
Although in the large intestine formation of villi is preceded by distinct longitudinal folds, it does not seem probable to me, after a study of my models, that there is a mechanical segmentation of the longitudinal folds. It must be remembered that the epithelial tube is ever growing by an increase in the number of its cells, and by the enlargement and duplication of its parts. Because of this active growth one would expect, therefore, villi to form by an active direct process, rather than by an indirect one. It seems more probable to me, that small knob—like elevations are developed along the tops of the folds, and that these knobs form into villi. If such were the case, the picture presented would always be one which would appear like a segmen— tation of folds. As the villi grew taller and taller, the segmenting fissures would appear to be sinking in deeper and deeper. It is important in this connection to note that the original folds are considerably smaller than the villi, a fact which is in favor of the view just proposed. Regarding the further development of villi, it may be said with certainty, that they arise separately in between those already present.
das basale Fiinftcl der Zotte cnthalt einen axialen, Blutgefasse fi‘1hrenden Bindegcwebstrang. Nur dieses basale Funftel bleibt erhalten
und geht in dcr Bildung der Lieberk1'ihn’schen Driisen auf, der grossere
Rest Wird zuruckgebildet-, er zerfallt.


It is certain that no such process as Schirman has described
takes place in the human large intestine.


The disappearance of villi is indeed diflicult to explain in
The earliest glands develop as small knob—like growths of the epithelium into the mesenchyma. As has been pointed out before, the additional glands are probably formed by a longitudinal splitting of those already present.
mechanical terms. All that can be said with certainty is that
the villi gradually develop, reach a certain maximum height,
and then gradually fade out. It is of interest in this connection,
however, to note that the effect of distention of the large intestine, caused by a storing up of meconium, brings about a disappearance, or at least a partial disappearance, of the villi. It
is hardly probable that mechanical distention of this kind is
connected with a lasting disappearance of villi of the large intestine, for they do not disappear permanently from the small
intestine, where distentions are also found.


Develnpmemf of the plicae semilunares coli
The villi reach their maximum height in embryos of 110 mm. to 140 mm. in length. From this stage on they gradually become smaller and smaller. A fusion of adjacent villi together at their bases, which gradually extends towards their apices and lengthens the intestinal glands, has been described by Koelliker (’61) and Schultze (’99) as the manner in which they disappear. Brand (’77) describes the connective tissue about the glands as the active factor in their disappearance. He believes that  the connective tissue gradually grows higher and higher, and in so doing, moulds the epithelium of the villi into that of the glands. Schirman (’98) describes the disappearance of the villi of the large intestine of the guinea-pig in an entirely different manner as follows:


The before described longitudinal and oblique folds of the
Die cmbryonalen Zotten des Dickdarms bestehen beim l\/leerschweinchen zu vier Funfteln ihrcr Liinge einzig aus Epithelzellen, nur das basale Fiinftcl der Zotte cnthalt einen axialen, Blutgefasse fi‘1hrenden Bindegcwebstrang. Nur dieses basale Funftel bleibt erhalten und geht in dcr Bildung der Lieberk1'ihn’schen Driisen auf, der grossere Rest Wird zuruckgebildet-, er zerfallt.
epithelium of the colon are in no Way related to the later plica.e
semilunares. They disappear with the development of villi, and
therefore, are only transient structures. The larger plicae se1ni—
lunares are of later origin, and as they run an oblique course
along the Wall of the intestine, they have been studied from both
cross and longitudinal sections. The observations shown in
table 1, have been made to indicate the condition of the inner
surface of the large intestine as regards these folds.
TABLE 1


Showing the dezvelopmem of the pl*[(:a,e swm'lun ares
It is certain that no such process as Schirman has described takes place in the human large intestine.


EMBRYO ASCENDING CoLox TRANSVEHSE COLON ”ESC"§‘T:\$:N(; ILIAC COLON
The disappearance of villi is indeed diflicult to explain in mechanical terms. All that can be said with certainty is that the villi gradually develop, reach a certain maximum height, and then gradually fade out. It is of interest in this connection, however, to note that the effect of distention of the large intestine, caused by a storing up of meconium, brings about a disappearance, or at least a partial disappearance, of the villi. It is hardly probable that mechanical distention of this kind is connected with a lasting disappearance of villi of the large intestine, for they do not disappear permanently from the small intestine, where distentions are also found.
mm.
65 2 large longitu- 3 large longitud. None
dinal folds folds
65 2 large and 1 2-3 very low None None
small longit. folds
fold
70 1-2 large folds 1 low broad
somewhat obli— fold
que
88 3 distinct longit 2-3 longit. folds Very low, but
folds broad circ.
folds, 0.09
to 0.13 mm.
high
99 1-2 longit. folds
110 Slight indication Slight indication
of folds of folds
120 None None None None
140 Oblique f old s,
0.09 mm. high,
0.90 mm. broad,
0.07-0.14 mm.
apart.
190 None (intestine Oblique f o 1 d s,
distended) 0.18-0.45 mm.
high, 0.27-0.36
mm. broad, 1.01.6 mm. apart.
240 Oblique fold s,
0.09-0.27 mm.
high, 0.36-0.90
In m. b r 0 a. d,
1 .2 — 1 .6 In In.
a.pa,rt.
320 None (intestine
distended) ‘
Tmos. Oblique folds, Oblique folds
foetus 0.36-0.54 mm. similar to those
high, 0.36 mm. in ascending
broad, 0.7-1.3 colon.
mm. apart.
Birth Oblique folds, Oblique fold s, Slight indica0.09 mm. high, 1.3‘ -3.0 mm. tion ofobli0.36--0.45 mm. high, 0.36-0.54 que folds
broad, 1.3-1.4 mm. br oad.
mm. apart (seen in cross


sections only)
Develnpmemf of the plicae semilunares coli


217
The before described longitudinal and oblique folds of the epithelium of the colon are in no Way related to the later plica.e semilunares. They disappear with the development of villi, and therefore, are only transient structures. The larger plicae se1ni— lunares are of later origin, and as they run an oblique course along the Wall of the intestine, they have been studied from both cross and longitudinal sections. The observations shown in table 1, have been made to indicate the condition of the inner surface of the large intestine as regards these folds.
218 FRANKLIN PARADISE JOHNSON


From table 1 it would appear that the earlier longitudinal
{{Johnson1913table01}}
folds which develop before the 120 mm. stage are lost. Later
oblique folds are formed which, owing to their course, position,
and constancy, must be the plicae scmilunares coli. These
folds, however, are not present in portions of the large intestine
which are distended, although the opposite View is held by some
regarding those of the adult.


THE VERMIFORM PROCESS


Early development
From table 1 it would appear that the earlier longitudinal folds which develop before the 120 mm. stage are lost. Later oblique folds are formed which, owing to their course, position, and constancy, must be the plicae scmilunares coli. These folds, however, are not present in portions of the large intestine which are distended, although the opposite View is held by some regarding those of the adult.


The history of the mucosa of the vermiform process in the
==The Vermiform Process==
human embryo is quite similar to that of the colon. One finds
first an epithelial tube with smooth walls and a round lumen.
Later as the tube grows in size, folds appear. The folds give
place to villi and glands develop. VVith the development of
glands the villi disappear. Unlike the glands of the colon,
however, those of the vermiform process oftentimes develop into
cysts, which degenerate, and thus cause a decrease in the number of glands. In the following brief description, numerous
references are made to the already described conditions of the
large intestine.


The early development of the vermiform process has been
===Early development===
described in connection with the early stages of the colon. In
the last—described stage (42 mm.) it is a simple tube of epithelium of about two to four cell nuclei in thickness, and presents
on its inner surface three or four slight ridges. At 55 mm. the
epithelial tube is decidedly large near its base (0.60 mm.), but
rapidly becomes smaller when followed towards its tip. The
epithelium of the basal portion is thrown into ridges which resemble very much those of the ascending colon of the same embryo.
A few vacuoles are present in some of the higher ridges. In
the base of the vermiform process of an embryo of 58 mm. (diameter only 0.40 mm.) the epithelial ridges are more numerous
They continue distalward for a short distance and gradually


fade out.
The history of the mucosa of the vermiform process in the human embryo is quite similar to that of the colon. One finds first an epithelial tube with smooth walls and a round lumen. Later as the tube grows in size, folds appear. The folds give place to villi and glands develop. VVith the development of glands the villi disappear. Unlike the glands of the colon, however, those of the vermiform process oftentimes develop into cysts, which degenerate, and thus cause a decrease in the number of glands. In the following brief description, numerous references are made to the already described conditions of the large intestine.
DEVELOPMENT ()F THE LARGE INTESTINE 219


At 65 mm. the base of the vermiform process measures 0.45
to 0.54 mm. in diameter. Its epithelium is now provided with
distinct villi which resemble those found in the ileum and ascending colon of the same stage. Followed distalward the vermiform process becomes somewhat smaller, but even to its end,
villi are present. In some places they appear to be forming from
longitudinal folds. The epithelium is everywhere simple columnar and has a thickness ranging from 0.028 to 0.042 mm. in
thickness, depending whether measured on tops of the folds or
between them. The large number of goblet cells present is
striking, there being by far a greater number in the vermiform
process than in the small or large intestine.


In an embryo of 88 mm. the diameter of the vermiform process at its base is about 0.45 mm. Numerous villi of about the
The early development of the vermiform process has been described in connection with the early stages of the colon. In the last—described stage (42 mm.) it is a simple tube of epithelium of about two to four cell nuclei in thickness, and presents on its inner surface three or four slight ridges. At 55 mm. the epithelial tube is decidedly large near its base (0.60 mm.), but rapidly becomes smaller when followed towards its tip. The epithelium of the basal portion is thrown into ridges which resemble very much those of the ascending colon of the same embryo. A few vacuoles are present in some of the higher ridges. In the base of the vermiform process of an embryo of 58 mm. (diameter only 0.40 mm.) the epithelial ridges are more numerous They continue distalward for a short distance and gradually fade out.  
same size as those in the lower part of the ileum at this stage
(0.25 to 0.27 mm. in height) are found. The glands have begun
to appear and in places Where they are cut in cross section they
show small round lumina. Toward its tip the villi are distinct,
but shorter (0.11 mm. high). Some are in the form of longitudinal folds (fig. 26). Glands are in most places very small,
but their beginnings are everywhere visible.


The epithelial tube of the base of the vermiform process in
an embryo of 110 mm. has a diameter of about 0.70 mm. Both
glands and villi are distinct, but the former are as yet very rudimentary. In most places they are, as well as can be determined
from cross and longitudinal sections, 0.09 to 0.11 mm. in length.
The villi are shorter than those found in the base of the Vermiform process of the preceding stage, being only 0.14 to 0.16 mm.
in height. Goblet cells are again very numerous. The distal
end has a diameter of 0.77 mm., being slightly greater than its
proximal portion. The villi are again shorter (0.11 to 0.13
mm.) than those found above, but somewhat longer than those
found in the same portion of the vermiform process of the preceding embryo. The glands are approximately the same length
as before. The extreme tip is rounded in shape, and is provided
with villi and glands of the same type as those on the side walls.
220 FRANKLIN PARADISE JOHNSON


Enlarged glands and gland cysts
At 65 mm. the base of the vermiform process measures 0.45 to 0.54 mm. in diameter. Its epithelium is now provided with distinct villi which resemble those found in the ileum and ascending colon of the same stage. Followed distalward the vermiform process becomes somewhat smaller, but even to its end, villi are present. In some places they appear to be forming from longitudinal folds. The epithelium is everywhere simple columnar and has a thickness ranging from 0.028 to 0.042 mm. in thickness, depending whether measured on tops of the folds or between them. The large number of goblet cells present is striking, there being by far a greater number in the vermiform process than in the small or large intestine.


In an embryo of 140 mm. the epithelial tube of tlie caecum
is 1.4 mm. in diameter, and its villi 0.18 mm. to 0.27 mm. high.
For the most part the glands are 0.09 to 0.13 mm. in length and
0.054 to 0.072 mm. in width. Some of the glands, however,
are swollen at their lower ends, being from 0.09 mm. to 0.13
mm. in diameter. They are all supplied with lumina, which
in the enlarged glands are occluded at the necks of the glands.
More distally, the base of the vermiform process has a diameter
of only 0.9 mm. The villi are similar to those of the caecum,
and the bulbous glands are more numerous. Still more distally,
near the tip of the vermiform process, the villi are shorter (0.14
to 0.16 mm.), and the enlarged glands are found in still greater
numbers. Figure 27, from a model of the epithelium of the tip
shows some of these glands. Many have enlarged ends connected with the surface epithelium by constricted necks. The
gland marked in the figure is the only gland which could be
found which is entirely cut off from the surface epithelium.
From serial sections, it is possible to make out that although
the bulb-like expansions are provided with decidedly large lumina,
these are totally out off from the lumen of the vcrmiform process.
Moreover, the cells of the necks of the glands appear to be undergoing degenerative changes. In many places only a slight
strand of tissue, largely composed of epithelial cell nuclei, could
be found connecting the bulb with the surface epithelium.


I11 the vermiform process of an embryo of 170 mm. the enlarged glands are very numerous. Owing, however, to poor
In an embryo of 88 mm. the diameter of the vermiform process at its base is about 0.45 mm. Numerous villi of about the same size as those in the lower part of the ileum at this stage (0.25 to 0.27 mm. in height) are found. The glands have begun to appear and in places Where they are cut in cross section they show small round lumina. Toward its tip the villi are distinct, but shorter (0.11 mm. high). Some are in the form of longitudinal folds (fig. 26). Glands are in most places very small, but their beginnings are everywhere visible.
preservation it is impossible to state whether they are connected
with the surface or not. In the connective tissue of the submucosa can now be seen distinct nodules of lymphoid tissue.


Sections through the base of the Vermiform process of an
embryo of 190 mm. shows ill-marked villi, 0.07 to 0.11 mm. in
height and of variable width. The glands, now 0.11 mm. to
0.16 mm. long, are more regular and only a few tend to be bulbous. The condition found is quite similar to that of the sigmoid
colon of the same embryo with the difference that there are
DEVELOPMENT or THE LARGE INTESTINE 221


fewer glands present. For the first time, the muscularis mucosae becomes Visible, arid the glands in places pierce it. In the
The epithelial tube of the base of the vermiform process in an embryo of 110 mm. has a diameter of about 0.70 mm. Both glands and villi are distinct, but the former are as yet very rudimentary. In most places they are, as well as can be determined from cross and longitudinal sections, 0.09 to 0.11 mm. in length. The villi are shorter than those found in the base of the Vermiform process of the preceding stage, being only 0.14 to 0.16 mm. in height. Goblet cells are again very numerous. The distal end has a diameter of 0.77 mm., being slightly greater than its proximal portion. The villi are again shorter (0.11 to 0.13 mm.) than those found above, but somewhat longer than those found in the same portion of the vermiform process of the preceding embryo. The glands are approximately the same length as before. The extreme tip is rounded in shape, and is provided with villi and glands of the same type as those on the side walls. 220 FRANKLIN PARADISE JOHNSON
tip of the vermiform process the epithelial tube is expanded to
a diameter of 1.7 mm., in comparison to 0.6 mm. at its base.
The villi have practically disappeared, only very slight elevations being left in places. The glands are similar in form, but
farther apart than those of the base. In places the muscularis
mucosae can be seen, but it is not well differentiated as yet.


In an embryo of 200 mm. the epithelial tube of the base of
===Enlarged glands and gland cysts===
the vermiferm process (fig. 28), although its diameter is about
the same (1.6 mm.), is quite different from that of the preceding stage. The villi have almost everywhere entirely disappeared. The glands are of Various size, some of the swollen
ones being 0.13 to 0.14 mm. broad. Most of these extend down
only to the muscularis mucosae, others have pushed into it and
cause it to bulge outward, while still others have pierced it. In
some places the swollen ends of glands appear as cysts, entirely
out off from the surface epithelium (figs. 10 and 2-8). Some cysts
appear to be entirely surrounded by a thin stratum of smooth
muscle derived from the museularis mucosae. The epithelium
li11ing the cysts shows various stages of degeneration. In some
it appears almost similar to the surface epithelium. In others
only that part of the epithelium lining the base of the cyst is
similar to that of the surface, while the upper portion, that is,
that portion of the cyst which had formerly been the neck of
the gland, has an epithelium which is much thinner and co111—
posed largely of broken dow11 nuclei and fragments of cell
protoplasm. In other cysts, degeneration has involved all the
cells of the epithelium, but those in the upper end again show
a more advanced stage of deterioration. Still other cysts are
of smaller size and have their epithelia reduced to a thin line.


Stohr C98) and Nagy (’11) found epithelial cysts of the kind
In an embryo of 140 mm. the epithelial tube of tlie caecum is 1.4 mm. in diameter, and its villi 0.18 mm. to 0.27 mm. high. For the most part the glands are 0.09 to 0.13 mm. in length and 0.054 to 0.072 mm. in width. Some of the glands, however, are swollen at their lower ends, being from 0.09 mm. to 0.13 mm. in diameter. They are all supplied with lumina, which in the enlarged glands are occluded at the necks of the glands. More distally, the base of the vermiform process has a diameter of only 0.9 mm. The villi are similar to those of the caecum, and the bulbous glands are more numerous. Still more distally, near the tip of the vermiform process, the villi are shorter (0.14 to 0.16 mm.), and the enlarged glands are found in still greater numbers. Figure 27, from a model of the epithelium of the tip shows some of these glands. Many have enlarged ends connected with the surface epithelium by constricted necks. The gland marked in the figure is the only gland which could be found which is entirely cut off from the surface epithelium. From serial sections, it is possible to make out that although the bulb-like expansions are provided with decidedly large lumina, these are totally out off from the lumen of the vcrmiform process. Moreover, the cells of the necks of the glands appear to be undergoing degenerative changes. In many places only a slight strand of tissue, largely composed of epithelial cell nuclei, could be found connecting the bulb with the surface epithelium.
described in the vermiform process of human embryos. According to Stohr the epithelium of the cut off glands becomes poorer
and poorer in goblet cells and begins to degenerate. The cyst
itself becomes filled with degenerative products, and as the
epithelium gradually goes to pieces the walls collapse. He
222 FRANKLIN PARADISE JOHNSON


Figs. 9 and 10 Cross sections of the Inueosa of the vermiform process (including the circular layer of the muscula.ri.s). Human embryo of 200 mm. X 120.
In figure 19 is shown at gland cyst not entirely out off from the surface epithelium.
In figure 10 is shown a cyst detached from the surface epithelium and undergoing
degenerative changes.


Fig. 11 Mucosa of the rectum (including the circular layer of the muscularis)
In the vermiform process of an embryo of 170 mm. the enlarged glands are very numerous. Owing, however, to poor preservation it is impossible to state whether they are connected with the surface or not. In the connective tissue of the submucosa can now be seen distinct nodules of lymphoid tissue.
in cross section. Human embryo of 65 mm. X 120. Shows several epithelial
gland cysts.
DEVELOPMENT OF THE LARGE INTESTINE 223


concludes: “Als letzten Rest der Druse findet man dann
minimale, ().()5—0.15 mm. messende Gruppen kleiner Epithelzellen,
die VOI1 einer dicken bindegewebigen Kapsel (Fig. 19a) umgeben
sind.”


Numerous and distinct lymphoid nodules are present in the
Sections through the base of the Vermiform process of an embryo of 190 mm. shows ill-marked villi, 0.07 to 0.11 mm. in height and of variable width. The glands, now 0.11 mm. to 0.16 mm. long, are more regular and only a few tend to be bulbous. The condition found is quite similar to that of the sigmoid colon of the same embryo with the difference that there are fewer glands present. For the first time, the muscularis mucosae becomes Visible, arid the glands in places pierce it. In the tip of the vermiform process the epithelial tube is expanded to a diameter of 1.7 mm., in comparison to 0.6 mm. at its base. The villi have practically disappeared, only very slight elevations being left in places. The glands are similar in form, but farther apart than those of the base. In places the muscularis mucosae can be seen, but it is not well differentiated as yet.
vermiform processes of all the embryos from 170 mm. up, but
never, so far as I have observed, are the cysts located in them.
I agree with Stéihr when he says: “Der Verfolg der Serie zeigt
immer, dass die reducirten Driisen nur am Rande des Knotchens liegen, zuweilen sogar in dessen Peripherie hineingepresst
sind. Das Centrum der Knotchen enthalt keine reducirten
Driisen.”


iVIoreoVer, such a degeneration of glands is not found in other
portions of the large intestine where lymphoid nodules are plentiful. It is not probable, therefore, that the development of
lymphoid tissue has anything to do with the formation and
degeneration of these cysts.


There are no marked changes in the form of the mucosa of
In an embryo of 200 mm. the epithelial tube of the base of the vermiferm process (fig. 28), although its diameter is about the same (1.6 mm.), is quite different from that of the preceding stage. The villi have almost everywhere entirely disappeared. The glands are of Various size, some of the swollen ones being 0.13 to 0.14 mm. broad. Most of these extend down only to the muscularis mucosae, others have pushed into it and cause it to bulge outward, while still others have pierced it. In some places the swollen ends of glands appear as cysts, entirely out off from the surface epithelium (figs. 10 and 2-8). Some cysts appear to be entirely surrounded by a thin stratum of smooth muscle derived from the museularis mucosae. The epithelium li11ing the cysts shows various stages of degeneration. In some it appears almost similar to the surface epithelium. In others only that part of the epithelium lining the base of the cyst is similar to that of the surface, while the upper portion, that is, that portion of the cyst which had formerly been the neck of the gland, has an epithelium which is much thinner and co111— posed largely of broken dow11 nuclei and fragments of cell protoplasm. In other cysts, degeneration has involved all the cells of the epithelium, but those in the upper end again show a more advanced stage of deterioration. Still other cysts are of smaller size and have their epithelia reduced to a thin line.
the Vermiform process in the subsequent stages of development.
At 240 mm. villi, bulbous glands, and cysts have entirely disappeared. The glands, as seen in figure 29, are small and rather
Widely separated. The muscularis rnueosae is distinct and oceasionally glands can be seen which have pierced it.


In specimens at seven months, birth, and a two Weeks old
child, practically the same conditions are found. Lymphoid
tissue, both in the diffuse and nodular form, is abundant. The
statement made by Berry and Lack (’06) that “In the vermiform appendix of the full term feotus there is practically no
lymphoid tissue, or at least so little as to constitute a negligible


quantity, Whilst lymphoid follicles are absent,” cannot be confirmed.
Stohr C98) and Nagy (’11) found epithelial cysts of the kind described in the vermiform process of human embryos. According to Stohr the epithelium of the cut off glands becomes poorer and poorer in goblet cells and begins to degenerate. The cyst itself becomes filled with degenerative products, and as the epithelium gradually goes to pieces the walls collapse. He concludes: “Als letzten Rest der Druse findet man dann minimale, ().()5—0.15 mm. messende Gruppen kleiner Epithelzellen, die VOI1 einer dicken bindegewebigen Kapsel (Fig. 19a) umgeben sind.”


'13:: AMERICAN .rotJI~cN.u. or ANATOMY, VOL. 14, N0. 2
224 FRANKLIN PARADISE JOHNSON


CONCLUSIONS


1. The large intestine, like the oesophagus, stomach, and
Figs. 9 and 10 Cross sections of the Inueosa of the vermiform process (including the circular layer of the muscula.ri.s). Human embryo of 200 mm. X 120. In figure 19 is shown at gland cyst not entirely out off from the surface epithelium. In figure 10 is shown a cyst detached from the surface epithelium and undergoing degenerative changes.
small intestine, is at first a simple tube of epithelium, and is the
last portion of the digestive tube to show distinctive changes
in the form of its mucosa. The first change which occurs is the
formation of longitudinal folds and ridges.


2. The ridges and folds first appear in the rectum and then
Fig. 11 Mucosa of the rectum (including the circular layer of the muscularis) in cross section. Human embryo of 65 mm. X 120. Shows several epithelial gland cysts.  
extend upward (orally). A second point of growth is found in
the ascending colon at the colic valve. The direction of growth
here is in the opposite direction (aborally). The transverse
colon is the last portion of the large intestine to develop ridges
and folds.


3. A few vacuoles similar to those found in the oesophagus,
stomach, and small intestine, are found in the epithelial wall of
the large intestine in its early stages.


4. The longitudinal folds are replaced by Villi in a manner
which suggests a segmenting of folds. However, it is not improbable that the villi of the large intestine arise after the manner
of those of the small intestine, as separate growths along the
tops of the folds.


5. Additional villi arise as separate growths between those
Numerous and distinct lymphoid nodules are present in the vermiform processes of all the embryos from 170 mm. up, but never, so far as I have observed, are the cysts located in them. I agree with Stéihr when he says: “Der Verfolg der Serie zeigt immer, dass die reducirten Driisen nur am Rande des Knotchens liegen, zuweilen sogar in dessen Peripherie hineingepresst sind. Das Centrum der Knotchen enthalt keine reducirten Driisen.”
Villi already formed, not being preceded by folds.


6. The first glands appear as knob—like protuberances of the
epithelium into the underlying mesenchyma. Additional glands
develop by a splitting, from below upwards, of those already
formed.


7. Villi reach their maximum height in embryos between 110
Moreover, such a degeneration of glands is not found in other portions of the large intestine where lymphoid nodules are plentiful. It is not probable, therefore, that the development of lymphoid tissue has anything to do with the formation and degeneration of these cysts.
mm. and 140 mm. in length. From this time on they gradually
become smaller in size. Remnants of them persist as folds
which form an irregular network in between the gland openings.
They are entirely’ gone at birth.


8. In the vermiform process villi and glands develop, and the
villi disappear at the same time and in the same manner as
those of the ascending colon.


9. Enlarged and cystic glands are found in the Veriniform
There are no marked changes in the form of the mucosa of the Vermiform process in the subsequent stages of development. At 240 mm. villi, bulbous glands, and cysts have entirely disappeared. The glands, as seen in figure 29, are small and rather Widely separated. The muscularis rnueosae is distinct and oceasionally glands can be seen which have pierced it.
process and eaecum. Many of them become detached from the
DEVELOPMENT OF THE LARGE INTESTINE 225


surface epithelium and are then entirely surrounded by connective tissue. They later disappear by degeneration and absorption. Lymphoid nodules are found in abundance in the vermi
form process at birth, but the cysts never lie in the centers of
them.


10. Epithelial cysts are also found in the mucosa of the rectum.
In specimens at seven months, birth, and a two Weeks old child, practically the same conditions are found. Lymphoid tissue, both in the diffuse and nodular form, is abundant. The statement made by Berry and Lack (’06) that “In the vermiform appendix of the full term feotus there is practically no lymphoid tissue, or at least so little as to constitute a negligible quantity, Whilst lymphoid follicles are absent,” cannot be confirmed.
They are in many Ways similar to those found in the vermiform
<br>
process, but differ from them in that they are not so deeply
{{Johnson1913table4}}
seated in the tuniea propria, are seldom entirely detached from
<br>
the surface epithelium, and disappear not by degeneration and
==Conclusions==
absorption, but by breaking through into the intestinal lumen.


11. Distention of the large intestine, due to the accumulation
# The large intestine, like the oesophagus, stomach, and small intestine, is at first a simple tube of epithelium, and is the last portion of the digestive tube to show distinctive changes in the form of its mucosa. The first change which occurs is the formation of longitudinal folds and ridges.
of meconium, brings about marked changes in the form of the
# The ridges and folds first appear in the rectum and then extend upward (orally). A second point of growth is found in the ascending colon at the colic valve. The direction of growth here is in the opposite direction (aborally). The transverse colon is the last portion of the large intestine to develop ridges and folds.
mucosa. It reduces its thickness, broadens and shortens both
# A few vacuoles similar to those found in the oesophagus, stomach, and small intestine, are found in the epithelial wall of the large intestine in its early stages.
villi and glands, and causes them to become spread apart.
# The longitudinal folds are replaced by Villi in a manner which suggests a segmenting of folds. However, it is not improbable that the villi of the large intestine arise after the manner of those of the small intestine, as separate growths along the tops of the folds.
# Additional villi arise as separate growths between those Villi already formed, not being preceded by folds.
# The first glands appear as knob—like protuberances of the epithelium into the underlying mesenchyma. Additional glands develop by a splitting, from below upwards, of those already formed.
# Villi reach their maximum height in embryos between 110 mm. and 140 mm. in length. From this time on they gradually become smaller in size. Remnants of them persist as folds which form an irregular network in between the gland openings. They are entirely’ gone at birth.
# In the vermiform process villi and glands develop, and the villi disappear at the same time and in the same manner as those of the ascending colon.
# Enlarged and cystic glands are found in the Veriniform process and eaecum. Many of them become detached from the surface epithelium and are then entirely surrounded by connective tissue. They later disappear by degeneration and absorption. Lymphoid nodules are found in abundance in the vermi form process at birth, but the cysts never lie in the centers of them.
# Epithelial cysts are also found in the mucosa of the rectum. They are in many Ways similar to those found in the vermiform process, but differ from them in that they are not so deeply seated in the tuniea propria, are seldom entirely detached from the surface epithelium, and disappear not by degeneration and absorption, but by breaking through into the intestinal lumen.
# Distention of the large intestine, due to the accumulation of meconium, brings about marked changes in the form of the mucosa. It reduces its thickness, broadens and shortens both villi and glands, and causes them to become spread apart.


BI BL IOGRAPHY
==Bibliography==


B.-‘:.(}INb‘KY, A. 1882 Un{.ersuch1u1gen fiber den Darmkanal dos mensehlichen
B.-‘:.(}INb‘KY, A. 1882 Un{.ersuch1u1gen fiber den Darmkanal dos mensehlichen Kindes. Arch. F. path. Anat., Bd. 89, pp. fi4—94.
Kindes. Arch. F. path. Anat., Bd. 89, pp. fi4—94.


BARTH 1868 Beitrage zur Iflntwickelung der Darmwand. Sitzungsb. d. Wien.
BARTH 1868 Beitrage zur Iflntwickelung der Darmwand. Sitzungsb. d. Wien. Akad. d. Wissensch., Bd. 58, pp. 128436.
Akad. d. Wissensch., Bd. 58, pp. 128436.


BERRY, J. M. 1900 On the development of villi in the human intestine. Anat.
BERRY, J. M. 1900 On the development of villi in the human intestine. Anat. Anz., Bd. 17, pp. 242-249.
Anz., Bd. 17, pp. 242-249.


BERRY, R. J. A., AND LACK, L. A. H. 1906 The vermiform appendix of man,
BERRY, R. J. A., AND LACK, L. A. H. 1906 The vermiform appendix of man, and the structural changes therein coincident with age. Jour. Anat. Physiol., vol. 40, pp. 2417-256.
and the structural changes therein coincident with age. Jour. Anat.
Physiol., vol. 40, pp. 2417-256.


BRAND, E. 1877 Beitréige zur Entwiekelung der Magen— und Darmwand. Verhandl. d. phys. -med. Gesellsch. zu Wi11‘zb., Bd. 9, pp. 243—256.
BRAND, E. 1877 Beitréige zur Entwiekelung der Magen— und Darmwand. Verhandl. d. phys. -med. Gesellsch. zu Wi11‘zb., Bd. 9, pp. 243—256.


JoHNsoN, F. P. 1910 The development of the mucous membrane of the oesophagus, stomach, and small intestine in the human embryo. Am. Jour.
{{Ref-Johnson1910}}
Anat., vol. 10, pp. 521-561.


KOELLIKER, A. 1861 Entwiekelungsgeschiehte des Menschen und der hoheren
JoHNsoN, F. P. 1910 The development of the mucous membrane of the oesophagus, stomach, and small intestine in the human embryo. Am. Jour. Anat., vol. 10, pp. 521-561.
'I‘hiere. Leipzig.
 
KOELLIKER, A. 1861 Entwiekelungsgeschiehte des Menschen und der hoheren 'I‘hiere. Leipzig.


1879 lbid. 2e Aufi.
1879 lbid. 2e Aufi.


LANGER, C. Von 1887 Ueber das Verh.-«1ltcn der Darmschleinihaut an de1' 1liocoecal-Klappe, nebst Bemerkungen fiber ihre Entwieklung. Denkschriften d. k. Akad. d. W. math.—natur\v. Classe, Bd. 54, Abt. 1, pp.
LANGER, C. Von 1887 Ueber das Verh.-«1ltcn der Darmschleinihaut an de1' 1liocoecal-Klappe, nebst Bemerkungen fiber ihre Entwieklung. Denkschriften d. k. Akad. d. W. math.—natur\v. Classe, Bd. 54, Abt. 1, pp. 51-58.
51-58.


LEWIS, F. T. 1911 Die Entwicklung (les Di<:kd:u'1ns. Handbllch der EntWiclzliingsgeschichte des Mensclien, herausgegeben Von Keibel und
LEWIS, F. T. 1911 Die Entwicklung (les Di<:kd:u'1ns. Handbllch der EntWiclzliingsgeschichte des Mensclien, herausgegeben Von Keibel und Mall. Rd. 2, siebzehntes T\"apitel, pp. 3824391. 226 FRANKLIN PARADISE JOHNSON
Mall. Rd. 2, siebzehntes T\"apitel, pp. 3824391.
226 FRANKLIN PARADISE JOHNSON


NAGY, L. V. 1911 Ueber die Histogenese des Darmkanals bci menschlichen
NAGY, L. V. 1911 Ueber die Histogenese des Darmkanals bci menschlichen Embryonen. Anat. Anz., Bd. 40, pp. l47~156. PATZELT, V. 1883 Ueber die Entwicklung der Diek(la.rIr1schleimhaut. Sitzungsb. d. k. Akad. d. Wissensch. Wien. Bd. 86, pp. 145472. SCHIRMAN, D. 1898 Ueber die Rtickbildung der Diekdarmzotten des Meerschweinchens. Verhandl. cl. phys.-med. Gesellsch. z. Wi1rzb., N.F., Bd. 32, pp. 1~9.
Embryonen. Anat. Anz., Bd. 40, pp. l47~156.
PATZELT, V. 1883 Ueber die Entwicklung der Diek(la.rIr1schleimhaut. Sitzungsb. d. k. Akad. d. Wissensch. Wien. Bd. 86, pp. 145472.
SCHIRMAN, D. 1898 Ueber die Rtickbildung der Diekdarmzotten des Meerschweinchens. Verhandl. cl. phys.-med. Gesellsch. z. Wi1rzb., N.F.,
Bd. 32, pp. 1~9.


SCHULTZE, O. 1899 Grundriss der Entwickclungsgeschichte des Menschen und
SCHULTZE, O. 1899 Grundriss der Entwickclungsgeschichte des Menschen und der Séiugethiere. Leipzig.
der Séiugethiere. Leipzig.


STo'HP., P. 1898 Uebcr die Entwicklung der Darmlymphknotchen und fiber
STo'HP., P. 1898 Uebcr die Entwicklung der Darmlymphknotchen und fiber die Riiclzbildung VOH Darmdrusen. Arch. f. mikr. Anat., Bd. 51, pp. 1—55.
die Riiclzbildung VOH Darmdrusen. Arch. f. mikr. Anat., Bd. 51, pp.
1—55.


VOIGT, J. 1899 Beitrag zur Entwickelung dcr Darmselileimhaut. Anat. Hefte,
VOIGT, J. 1899 Beitrag zur Entwickelung dcr Darmselileimhaut. Anat. Hefte, Abt. 1, Bd. 12, pp. 4940.
Abt. 1, Bd. 12, pp. 4940.


PLATE 1
==Plates==


EXPLANATION OF FIGURES
===Plate 1===


12 Wax reconstruction of the epithelium of the ascending colon. Human
12 Wax reconstruction of the epithelium of the ascending colon. Human embryo of 50 mm. X89.
embryo of 50 mm. X89.


13 Wax reconstruction of the epithelium of the transverse colon. Human
13 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 50 mm. X 89.
embryo of 50 mm. X 89.


14 Wax reconstruction of the epithelium of the descending colon. Human
14 Wax reconstruction of the epithelium of the descending colon. Human embryo of 50 mm. X 89.
embryo of 50 mm. X 89.


15 Wax reconstruction of the epithelium of the ascending colon (portion near
15 Wax reconstruction of the epithelium of the ascending colon (portion near the colic valve). Human embryo of 58 mm. X 89.
the colic valve). Human embryo of 58 mm. X 89.


16 Wax reconstruction of same. More caudad portion. X 89.
16 Wax reconstruction of same. More caudad portion. X 89.


17 Wax reconstruction of the epithelium of the transverse colon. Human
17 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 58 mm. X 89.
embryo of 58 mm. X 89.
 
18 Wax reconstruction of the epithelium of the descending colon. Human
embryo of 58 mm. X 89.


PLATE 2
18 Wax reconstruction of the epithelium of the descending colon. Human embryo of 58 mm. X 89.


EXPLANATION OF FIGURES
===Plate 2===


19 Wax reconstruction of the epithelium of the upper part of the rectum.
19 Wax reconstruction of the epithelium of the upper part of the rectum. Human embryo of 58 mm. X 89; ac, epithelial gland cyst.
Human embryo of 58 mm. X 89; ac, epithelial gland cyst.


20 Wax reconstruction of the epithelium of the transverse colon. Human
20 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 65 mm. X 89.
embryo of 65 mm. X 89.


21 V5/ax reconstruction of the epithelium of the descending colon. Iluman
21 V5/ax reconstruction of the epithelium of the descending colon. Iluman embryo of 65 mm. X 89.
embryo of 65 mm. X 89.


22 Wax reconstruction of the epithelium of the sigmoid colon. Human em~
22 Wax reconstruction of the epithelium of the sigmoid colon. Human em~ lbryo of 190 mm. X 89.
lbryo of 190 mm. X 89.


===Plate 3===


PLATE 3


EXPLANATION OF FIGURES
23 Wax reconstrmtinn of the epithelium of the transverse colon. Human embryo of 99 mm. X 89.


23 Wax reconstrmtinn of the epithelium of the transverse colon. Human
24 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 140 mm. X 89.
embryo of 99 mm. X 89.


24 Wax reconstruction of the epithelium of the transverse colon. Human
25 Wax reconstruction of the epithelium of the transverse colon. Human embryo at birth. X 178.
embryo of 140 mm. X 89.


25 Wax reconstruction of the epithelium of the transverse colon. Human
embryo at birth. X 178.


===Plate 4===


PLATE 4
26 Wax reconstruction of the epithelium of the tip of the vermiform process. Human embryo of 88 mm. X 89.
EXPLANATION OF FIGURES


26 Wax reconstruction of the epithelium of the tip of the vermiform process.
27 Wax reconstruction of the epitheliuni of the tip of the vcrmiform process‘ Human embryo of 140 mm. X 89; :1}, epithelial gland cyst, entirely out ofi from surface epithelium.
Human embryo of 88 mm. X 89.


27 Wax reconstruction of the epitheliuni of the tip of the vcrmiform process‘
28 Wax reeonstructioii of the epithelium of the base of the vermiform process. Human embryo of 200 mm. X 89; 3:, epithelial gland cyst, entirely out off.
Human embryo of 140 mm. X 89; :1}, epithelial gland cyst, entirely out ofi from
surface epithelium.


28 Wax reeonstructioii of the epithelium of the base of the vermiform process.
29 Wax reconstruction of the epithelium of the tip of the vermiform process. Human embryo of 240 mm. X 89.
Human embryo of 200 mm. X 89; 3:, epithelial gland cyst, entirely out off.


29 Wax reconstruction of the epithelium of the tip of the vermiform process.
{{Footer}}
Human embryo of 240 mm. X 89.
[[Category:Gastrointestinal Tract]][[Category:Intestine]][[Category:Historic Embryology]][[Category:1910's]][
[[Category:Harvard Collection|Harvard Collection]][[Category:Draft]]

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Johnson FP. The development of the mucous membrane of the large intestine and vermiform process in the human embryo. (1913) Amer. J Anat., 14: 187-233.

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This historic 1913 paper by Franklin Paradise Johnson (1888-1943) describes the development of the mucous membrane of the large intestine and vermiform process in the human embryo. In this paper he describes embryos and wax models from the Harvard Embryological Collection.



Other papers by this author: Template:Ref-Johnson1910b

Johnson FP. The development of the rectum in the human embryo. (1914) Amer. J Anat. 16(1): 1-58.
See also Frederic Lewis's 1943 tribute to Johnson: Lewis FT. Clark ER. and Scammon RE. Franklin Paradise Johnson. (1943) Anat. Rec. 86: 1-7.

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The Development Of The Mucous Membrane Of The Large Intestine And Vermiform Process In The Human Embryo

Franklin Paradise Johnson

From The Harvard Medical School, Boston

Twenty-Nine Figures

The following paper is .the second of a series of studies concerning the mucous membrane of the digestive tract. The first (Johnson ’lO) dealt with the development of the oesophagus, stomach and small intestine. The present paper is devoted entirely to the large intestine, and includes all its parts except the lower portion of the rectum. It is followed by an account of the effects of distention upon the small and large intestines of various animals. It is proposed to publish later an account of the development of the anal portion of the rectum, work upon which is nearly completed. The study of the mucous membrane of the digestive tract was proposed to me by Dr. F. T. Lewis in 1909, and as the work has progressed, I have received from him many valuable suggestions.

The development of the large’ intestine is of special interest owing to the variety of pictures its mucosa presents. Relatively simple in the beginning and again in the adult as compared with other portions of the alimentary canal, the mucosa passes through a number of complicated changes before it attains its full development. To begin with, the smooth epithelial tube of the large intestine develops more or less regular longitudinal folds. These folds, as will be subsequently described, are later replaced by villi. Still later the villi themselves disappear. Meanwhile, glands are forming, and when the villi have entirely faded out, the large intestine reaches its adult condition. The presence of ‘transitory’ villi has long been known, being first described by Barth in 1868. Since then they have been studied by a number of investigators, and several opinions have arisen in regard to their manner of disappearance. However, most of the former work has been done on lower animals, no one account giving a complete history of the changes that take place in the human embryo.


In the present paper an attempt is made to describe in some detail the mucosa of the large intestine and vermiform process in a number of consecutive embryonic stages, and to present a series of pictures made from wax reconstructions illustrating the descriptions. The following account deals strictly with the human embryo, and is based on a number of carefully selected stages. The embryos used are arbitrarily divided into two groups ;—the younger stages, which were sectioned whole; and the older stages, from which the various portions of the digestive tube were removed from the embryo and sectioned separately. The younger stages used were all obtained from the Harvard Embryological Collection. They are as follows:

Crown-Rump Length (mm) Harvard Embryological Collection Series no. Fixation
7.5 256 Zenker’s fluid
10.0 1000 Zenker’s fluid
16 .0 1322 Picro-sulphuric
22.8 871 Alcohol and formalin
30.0 913 Formalin
37.0 820 Parker’s fluid
42.0 838 Zenker’s fluid
Reference: Johnson FP. The development of the mucous membrane of the large intestine and vermiform process in the human embryo. (1913) Amer. J Anat., 14: 187-233.


The older stages were obtained from three different collections. I Wish here to express my thanks to Prof. C. S. Minot, Harvard Medical School, Prof. C. M. Jackson, University of Missouri, and Prof. Franz Keibel, Freiburg i/Br., for allowing me the privilege of cutting out what portions of their embryos I desired for my work. The list of older stages used is as follows:

Crown-Rump Length (mm) Fixation Collection Series no.
50 Zenker’ s fluid Keibel
55 Alcohol Minot 249
58 Zenker’ s fluid Keibel
65 Zenker’s fluid Keibel
70 Alcohol Keibel
73 Picro-sulphuric Minot 116
75 Alcohol Minot 110
88 Formalin Jackson 137
99 Alcohol Minot 340
110 Formalin Jackson 143
120 Zenker’ s fluid Minot 342
140 Formalin Jackson 263
170 Formalin Jackson 222
187 Formalin Minot 315
190 Formalin Jackson
200 Formalin Jackson 89
240 Muller’s Fluid Minot 186
320 Formalin1 Jackson 16
Birth2 Zenker’s fluid Minot 345
Birth3 Zenker’s fluid Minot 341
Two weeks child4 Zenker’s fluid Mlinot

1 First injected with a mixture of phenol, alcohol, glycerino, and formalin
2 Premature birth at seven (?) months. Lived thirty minutes
3 Normal fetus at birth
4 Premature at seven months. Lived two weeks

Reference: Johnson FP. The development of the mucous membrane of the large intestine and vermiform process in the human embryo. (1913) Amer. J Anat., 14: 187-233.


The Large Intestine

Early development

In an embryo of 7.5 mm. the large intestine, like the oesophagus, stomach, and small intestine of the same embryo‘, is a simple tube of epithelium surrounded by mesenchyma. It is continuous, without demarction, with the small intestine above, and with the urogenital sinus below. Its cephalic end is indistinctly indicated by a slight swelling, which is regarded by Lewis (’11) as the beginning of the Vermiform process. This swelling, which I will designate by the term ‘colic ampulla’ (ampulla coli), is spindle-shaped and has a diameter (measured from side to side in its widest place) of 0.07 mm. Below the swelling the tube becomes markedly narrower. In its narrowest portion it measures but 0.04 mm. in diameter. As the urogenital sinus is approached the epithelial tube again increases in size and becomes compressed from side to side. This enlargement passes insensibly over into the epithelium of the cloaca.


The walls of the epithelial tube also vary in thickness. Above, where it is broadest, the walls have a thickness of about 0.028 mm. and are composed of cells which have no distinct cell boundaries. Three rows of oval nuclei are discernible. In the narrower middle portion the walls average about 0.017 mm. in thickness, and show only two rows of nuclei. Where the tube is expanded in the cloacal region, the epithelium is approximately of the same thickness as in the colic ampulla. The lumen in most places is a narrow slit-like cleft, larger in the extremities than in the rnid—region of the large intestine, but everywhere present and patent. It communicates with the larger lumen of the cloaca, but cannot be traced through this to the outside because of the presence of the cloacal membrane.


In an embryo of 10 mm. the large intestine presents practically the same relations, but shows a marked increase in size. The colic ampulla, which is now situated well out in the coelom of the umbilical cord, measures alout 0.33 mm. in diameter, and has an epithelium 0.045 mm. in thickness. A slight budlike protuberance of almost the same size as the swelling itself, arises from it, and extends into the mesenchyma. Followed caudally, the epithelial tube of the large intestine quickly diminishes in size, and continues of small size until the region of the rectum is reached. Here it presents another spindle—shaped swelling. This swelling is connected with the cloaca by a short and narrow tube. The upper narrow portion of the epithelial tube measures about 0.07 mm. in diameter, and its wall is 0.028 mm. thick. The swelling is’ 0.12 mm. in diameter, and has a wall thickness of 0.036 mm. The lumen is continuous as far as the cloacal membrane where it is closed ofi“ from the exterior.

At 16 mm. the colic ampulla is similar in form but larger than in the preceding stages, being now 0.17 mm. in diameter. It

is directly continued into the Vermiform process, which is found in the umbilical cord, pointing away from the embryo. Large at its base where it joins the colic ampulla, the vermiform process tapers gradually towards its blind end. The before-mentioned narrow portion of the large intestine, now 0.09 mm. in diameter, has increased much in length. The lumen of the lower end of the digestive tube no longer leads into the cloaca, but opens to the outside by an extremely small aperture.

In the further course of its development, the swelling in the rectal region becomes much larger, and longitudinal folds make their appearance. These longitudinal folds increase in numbers, and are markedly constant in position in all the older stages. Just what is the fate of these folds I am unable at the present time to state precisely, but it is not improbable that they give rise to the rectal columns (columnae rectales Morgagni) while the spaces between them no doubt develop into the rectal sinuses (sinus rectales). A discussion of the further development of this portion of the digestive tract, however, has been omitted from the present paper.

The development of longitudinal folds

In an embryo of 22.8 mm. one sees for the first time a change in the form of the epithelium. In the colic ampulla, which now has a diameter of 0.20 mm., the epithelium shows three low longitudinal ridges on its inner surface. These ridges also extend for short distances into the colon and vermiforrn process.

It becomes necessary at this point to explain the manner in which the terms ‘ridges’ and ‘folds’ have been used throughout the remainder of this article. The term ‘ridge’ has been employed to designate a thickening of the epithelium which projects into the lumen. It must have no corresponding indentation on its under surface into which mesenchyma would extend. By a ‘fold’ is meant a projection with an indented basal surface, into which the underlying mesenchyma protrudes. This distinction is desirable, as its usage makes it possible to explain in few words the shape of the basal surface of the epithelium along with that of its free surface.


The epithelium in the embryo under consideration (22.8 mm.) varies in thickness in different regions. In the colic ampulla and vermiform process it is 0.056 mm. thick and shows three to four rows of nuclei. In the remainder of the colon down to the rectal ampulla, it is only 0.034 mm. in thickness and shows but two to three rows of nuclei. At no place are the boundaries between the cells distinct, but the free and basal surfaces are well marked.

In an embryo of 30 mm. the whole of the vermiform process and the valve of the colon lie in the coelom of the umbilical cord. An examination of the interior of the colon in this region shows the beginnings of two to three epithelial ridges. These Vary in height, the epithelium being 0.070 mm. thick, measured through the summit of the largest ridge, while in the depressions between them, it is only about 0.028 mm. thick. Three or four rows of nuclei can be made out. The remainder of the colon has an average diameter of 0.15 mm. Throughout its great length the epithelial tube is still cylindrical in shape, having a wall 0.048 mm. in.thickness. Three or four rows of nuclei are present.

At 37' mm. the whole of the vermiform process still lies in the umbilical cord. The epithelial ridges are higher than in the former stages. In the base of the vermiform process there are four of these, in the middle only three; in the beginning of the colon, three or four. The highest ridge measures about 0.10 mm. in height and has three or four rows of nuclei. Between the ridges the epithelium is only 0.042 mm. thick and shows but two or three nuclear layers. The remainder of the large intestine gradually decreases in size when followed caudally. The portion which is to become the ascending colon is 0.27 mm. in diameter; the transverse 0.22 mm.; and the descending colon 0.18 mm. The epithelium is about 0.056 mm. thick in all these portions. A few vacuoles, such as have been found in the epithelial walls of the stomach and oesophagus are present in the colon of this embryo.


In an embryo of 42 mm. the ridges of the epithelium are in part replaced by true longitudinal folds. In the Vermiform process and ascending colon three to four of these are present; in the transverse colon two to three; in the greater part of the descending colon three; while in the remainder of the descending colon five to six more irregular ones. These folds vary in height from 0.014 to 0.028 mm. The epithelium is thicker on their crests than between them. It presents an appearance which is largely in accordance with a condition which Patzelt (’83) has found in the large intestine of the cat embryo. He describes two types of cells. In the corners of the star-shaped lumen the cells are short and broad, and have basal nuclei which stain intensely with haemotoxylin. The cells of the ‘second type are found on the tops of the folds. They are longer, finely granular, and somewhat denser. Their nuclei are long—oval or drop-shaped and stain more intensely than those of the first type. The for~ mer groups of cells he states are the first anlagen of the Lieberkiilin glands; the latter of the villi. The epithelium of the large intestine of the embryo under consideration (42 mm.) has been described and pictured by Lewis (’11). The two types of cells are found arranged in separate groups, but, however, are not as distinct as those of the cat described by Patzelt.


In the ascending colon of an embryo of 50 mm., the epithelial tube has a diameter of about 0.23 mm., and shows four distinct longitudinal folds. These are, as shown in figure 12, rounded on their tops, and are of different heights, the largest measuring about 0.06 mm. In the piece of ascending colon sectioned for study, which measures about 0.7 mm. in length, the epithelial tube changes but little in shape, the four distinct longitudinal folds running throughout. The epithelium, which has an aVer~ age thickness of 0.050 mm., is columnar, and, as seen in sections ten microns thick, is apparently stratified, being composed of two or perhaps three, layers of cells. The nuclei, which are oval in shape, are all placed in a zone midway between the free and basal surfaces of the epithelium, there being a clear zone of protoplasm on either side. A definite cuticular border is everywhere present on the free surface of the epithelium. Two distinct types of cells are not visible. Outside of the epithelium is a zone of loose mesenchyma which is bounded by a thin layer of myoblasts, the circular layer of the muscularis. This is in turn bounded by a layer of mesenchyma and surrounding the whole, except at its mesenteric attachment, a distinct serous epithelium is seen.


In passing ab-orally from the ascending colon into the transverse colon, one of the four longitudinal folds just described drops out, while a second becomes so much reduced in size that it is scarcely recognizable as a fold (figs. 1 and 13). The two remaining folds are distinct andabout 0.06 mm. in height. The epithelial tube has a diameter of about 0.27 mm. The remaining features of this portion of the large intestine are similar to those of the ascending colon.

First appearance of goblet cells

In the iliac colon (50 mm. embryo), the epithelial tube as a whole is flattened from side to side. Its greater diameter is 0.36 mm., its lesser 0.18 mm. A considerable change in the condition of folds is evident. They are shallow, irregular, and more numerous than in the ascending and transverse colons. A model of a small portion of this region is shown in figure 14. The distinction between epithelial ridges and folds is here apparent——only those protuberances, which have indented basal surfaces into which the mesenchyma extends, being considered as true folds. Measured through the ridges the epithelium is in places 0.084 mm. thick, while in the clefts between them, it is only 0.028 mm. thick. The two types of cells described by Lewis in the 42 mm. stage are distinct. A few cells on the ridges have a protoplasm .which is clearer than others, and are shaped somewhat like goblet cells. Because these cells in the next few stages take on more and more the appearance of goblet cells until their identity cannot be doubted, I believe them to be goblet cells in a very early stage of differentiation. Voigt (’99) was able to distinguish goblet cells first in the rectum of a human embryo of 70 mm.


The ascending colon of an embryo of 55 mm. has a diameter’ of 0.45 mm. Ten to twelve longitudinal ridges are found, but distinct folds are absent. The ridges are irregular in form and of varying size, the largest being about 0.10 mm. in height. The two types of cells are distinct now in this region of the large intestine, some of which are like those which Patzelt has described as drop-shaped. In many places large vacuoles similar to those described above are found in the epithelium of the ridges.


The epithelial tube of the transverse colon is of the same size as the ascending, and shows six well marked projections into the lumen, two of which are folds. In the upper part of the descending colon, two ridges and two folds are present. In the iliac colon the folds drop out and only ridges are found. When followed downward, the descending colon shows more and more ridges and when the sigmoid colon is reached there are as many as ten or twelve. Still more caudally the rectum shows folds which have taken the place of the ridges. In the lower part of the rectum, just above the rectal arnpulla, practically all the ridges have been replaced by folds, varying from ten to fourteen in number. The appearance obtained from cross sections, therefore, is somewhat similar to that found in the stomach of the same and slightly older embryos—the clefts in between the ridges corresponding to the gastric pits. The clefts, however, are broader and the cells of the epithelium lining them are more columnar in form than those of the gastric pits. Throughout all these portions of the large intestine the cells on the crests of the ridges differ from those between them. In the rectum the epithelium is distinctly one-layered. On the crests of its folds it presents a number of cells with clear protoplasm and basal nuclei. These presumably are developing goblet cells. In the colon of an embryo of 58 mm. the epithelial tube is found to be quite similar to that of the 55 mm. embryo just described. It is slightly smaller throughout than in the previous stage, which difference may in part be accounted for by the different kinds of preserving fluids used. In the cephalic end of the ascending colon the epithelial tube has now a diameter of 0.38 mm. and shows numerous ridges and folds as seen in figure 15. More caudally in the ascending colon the epithelium is not so irregular as near the eaecum. As seen in sections three folds and one ridge are present. Figure 16 shows a model of this portion of the intestine. It is to be noted that the tops of the longitudinal folds are irregular in form. The diameter of this region of the glit is about 0.36 mm., while the epithelium averages about 0.050 mm. in thickness.

  • 1 In this and all remaining text figures certain histological details -“have been omitted.


Fig. 11 Cross section of the transverse colon of a human embryo of 50 mm. X 60.




Fig. 2 Cross section of the transverse colon of a human embryo of 58 mm. X 60.


The transverse colon of an embryo of 58 mm. shows six distinct folds, as seen in figure 2. A model of one half of the tube of this region is represented in figure 17. The diameter of the epithelial tube averages 0.38 mm. The descending colon (fig. 18) has a diameter of 0.34 mm., is more rounded in shape, being quite similar to the more cephalic part of the ascending colon. The crests of the folds and ridges are, however, not so angular.

First appearance of villi

In the rectum the epithelial folds have increased in size and give to the lumen a very irregular form. As shown in figure 19, some of the folds run almost transversely. The presence of transverse folds have been noted in the lower portion of the rectum in a number of older embryos as well. Besides folds, here and there are present conical—shaped projections of the epithelium. These represent the first transitory villi of the large intestine.


In a number of places the folds seem to be fused together at their tops, shutting off small rounded spaces. These spaces I have determined from serial sections to be epithelial cysts. They are found in corresponding portions of the rectum of other embryos, but are confined to this region of the large intestine alone. A portion of one of these cysts is shown in figure 19 at ya. They are described in detail below.


At this point it seems advisable to make the following summary regarding the development of ridges and folds. In the beginning the epithelial tube is cylindrical in shape. The first changes that take place in its form are found in the rectum, where it shows a number of longitudinal ridges. These ridges are the forerunners of folds, for everywhere they later appear as if pushed in from behind by the underlying mesenchyma. Soon afterward ridges and folds are found in the descending colon, the direction of growth being from below upward. However, before these changes have extended into the transverse colon, similar changes are found to be occurring in the ascending colon near to the colic valve. The direction of growth here is opposite that in the descending colon, that is, ab-orally. The transverse colon is, therefore, the last portion of the large intestine to develop folds. Similarly, in a few of the subsequent stages, the transverse colon shows a slight retardation in the development of villi and glands as compared with the rectum, descending and ascending colons. However, this retardation is soon overcome by an increased rate in growth, and then conditions found in all parts of the large intestine are quite similar. As a matter of convenience and simplicity, the development of the transverse colon has been described most completely in the remainder of this article, and other portions of the large intestine are described, as far is possible, from a comparative point of View with respect to it.


Fig. 3 Cross section of the transverse colon of a human embryo of 65 mm. X 60.

The transverse colon of an embryo of 65 mm. differs considerably from that of the embryo just described. The epithelial tube is circular in section and measures 0.54 mm. in diameter. In transverse section (fig. 3) eighteen to twenty-three projections are seen extending into the lumen. VVl1en modelled these projections are seen to be longitudinal folds and villi as shown in figure 20. The villi are everywhere arranged in longitudinal ows, suggesting that the folds have become broken up into segments. The folds and villi measure from 0.08 to 0.11 mm. in height and are usually between 0.07 and 0.11 mm. in width at their bases. The epithelium on their tops is distinctly simple columnar in form, and is reduced to 0.019 mm. in thickness; between the folds it is 0.031 mm. thick.


Numerous villi are found in the ascending colon. A comparison of these with those villi in the lower part of the ileum shows that the two are quite similar in form and size. At a short distance from the colic valve, the epithelial walls of the ascending colon become pushed in by three large Inesenchymal folds, reducing the lumen to a narrow Y—shaped cleft. Here are found folds and villi resembling those shown in figure 20. The descending colon is smaller in diameter than the transverse, being only 0.45 mm. An examination of its inner surface (fig. 21), shows folds and villi, and what apparently are partially formed villi, about eight to nine rows in all. These are longer than those of the transverse colon, 0.17 to 0.22 mm., but of about the same width. In the sigmoid colon is found a condition comparable to that of the descending colon. However, goblet cells are far more numerous.

First appearance of intestinal glands

The epithelial tube of the upper portion of the rectum (embryo of 65 mm.) is flattened from side to side, and measures 1.17 by 0.77 mm. in cross section. A very different appearance is presented from that of the transverse colon. The epithelial wall is bent into a number of folds which are closely packed together. Many of these measure as much as 0.27 and 0.36 mm. in height. The bottoms of the spaces between these projections are developing glands. Where they are cut obliquely or in cross section their basal ends are seen to be tubular in form and provided with small round lumina. '


Epithelial cysts are more numerous than in the preceding embryo. They represent glands and intervillous spaces which have become closed over at their tops. They show evidences of internal pressure by their bulbous appearance and by the flattening of the lining epithelium of the more superficially lying part of the cyst (fig. 11). In many respects these cysts are similar to those found in the vermiform process (compare fig. 11 with figs. 9 and 10) but differ from them by their more superficial position and in that they can rarely be considered to be entirely separated from the surface epithelium. Moreover, they have a different fate from those of the vermiform process. Instead of the epithelium entirely degenerating, the cyst collapsing, and finally being absorbed, the cysts of the rectum open up with the intestinal lumen and become glands again, at least this interpretation seems justifiable, since the cysts gradually disappear Without showing such degenerative processes as are easily recognizable in those of the vermiform process.


The condition found in the transverse colon of an embryo of 70 mm. is not much in advance of the same portion of the large intestine at 65 mm. Its epithelial tube has a diameter of 0.54 mm. The lumen is relatively large and the villi project into it 0.09 to 0.13 mm. The cells forming the epithelium are tall columnar, 0.025 in height, and contain at their basal ends, elongated nuclei. The protoplasm, which stains decidedly yellow with orange—G, appears to be mucous in character. Here and there swollen goblet cells are seen. A small portion of the sigmoid colon presents an appearance similar to that described in the rectum at 65 mm. It measures 0.54 mm. by 0.72 mm., and contains folds and villi 0.23 to 0.27 mm. in height. Epithelial glands and cysts are found in large numbers. In the rectum the same conditions are presented, although the epithelial tube is larger and the villi taller (0.25 to 0.32 mm.). The latter seem, however, to be so fused together that they appear in many places as irregular running folds. Goblet cells are everywhere numerous.


In-a well preserved transverse colon of an embryo of 73 mm. the epithelial tube measures 0.58 mm. in diameter. The villi and folds, some of which are now 0.22 to 0.23 mm. high, decrease to a marked extent the size of the lumen. In width the villi show a slight increase, being 0.09 to 0.18 mm. through at their bases. The tops of the villi are in many places so closely approximated that it is quite impossible from cross sections of this stage alone to determine whether an actual fusion has or has not taken place. Because of this condition, which I believe to have been brought about by a strong contraction of the muscularis, an attempt to model these villi accurately proved fruitless. From the conditions found in the large intestine, of other embryos of about the same age, however, it would not seem probable that such a thing as an actual fusion had taken place. The epithelium on the tops of the projections is distinctly one-layered and 0.025 to 0.028 mm. thick, while between them it appears two—layered, and is almost twice as thick, 0.042 to 0.052. Only the portions of the epithelium in between villi are provided with distinct basement membranes.


Fig. 4 Cross section of the transverse colon of a human embryo of 88 mm. X 60.

In the descending colon practically the same conditions are repeated, with the exception that a few more villi are present.

In the transverse colon at 75 mm., even though considerable shrinkage is present, the villi are seen distinctly separated from one another. Other portions of the large intestine from the two last—mentioned embryos were not obtained.

In the transverse colon of an embryo of 88 mm. (fig. 4), are found numerous villi, which are arranged so that they form longitudinal rows. The epithelium on the tops and sides of the villi is similar to that of the preceding stages, being simple columnar in form and containing goblet cells. Between the villi the cells are tall cylindrical and conical in shape, contain oval nuclei which seem to be closely crowded together, and stain intensively. These groups of cells form small knob-like projections and are the beginnings of the intestinal glands.


In the ascending, descending, and sigmoid eolons, as seen from transverse and longitudinal sections, both villi and the beginnings of glands are distinguishable. The villi graduall_v increase in length as the large intestine is followed caudally; thus in the ascending colon they are about 0.14 to 0.16 min. in height; in the transverse, 0.18 to 0.20 min.; in the descending colon, 0.22 to 0.25 mm.; in the sigmoid, 0.27 to 0.32 mm.; while in the rectum, 0.27 to 0.36 mm. In many places their apices are in close contact with each other, appearing as though fused. Likewise, the glands show a more advanced stage of growth as the large intestine is followed downward. In the ascending colon they are scarcely visible; in the rectum they are very distinct. Except for this more advanced stage of development, conditions in the rectum are not so strikingly different from those in the remainder of the colon as at a former period. The epithelial cysts, while not so numerous, have not entirely disappeared. Those few which remain are smaller and are confined to the lower part of the rectum.


In an embryo of 99 mm. the transverse colon shows numerous villi arranged in rows, 20 to 25 in number. As seen in figure 23, few distinct folds are present, but these do not occur in any definite relation to the villi, that is, the rows of villi and the folds are not alternately placed around the Wall of the intestine. From this and from what I have seen in other embryos, it seems improbable that the new villi, which are now arising at a very rapid rate, are preceded by folds. hfore probably they develop after the manner of the villi in the small intestine, as separate growths between the villi already formed.


Numerous gland buds are also present in the specimen as shown in figure 23. “7 here the glands are cut in cross section, they show small but distinct lumina, surrounded by columnar cells of the mucous variety, many of which are goblet cells. On the tops and sides of the villi the epithelial cells are 0.022 to 0.028 mm. in height while in the glands they are 0.034 to 0.042 mm. Although shrunken from the underlying mesenehyma, the epithelial tube has increased to 1.03 mm. in diameter. The sigmoid colon has a diameter of 0.95 mm. and an epithelium which is similar in variety and of equal thickness to that just described.


From this point on, measurements taken of the glands and villi can only be considered approximately accurate. This is due to the fact that there is no sharp line of demarcation between gland and villus, consequently one is unable to determine just where the gland begins and where the villus leaves ofl'. A similar difliculty was met with in the ease of the small intestine. It is, however, possible, with the aid of models for comparison,


Fig. 5 Cross section of the transverse colon of a human embryo of 110 mm. X 60.

to judge the line of division approximately. In the following account of the growth of glands and villi, the figures given are the average of a number of measurements made from cross or longitudinal sections, or in some cases, from both. A more accurate method, which was employed whenever possible, was the direct measurement of these structures from the models themselves. In the transverse colon of the embryo under de~ scription (99 mm.), the glands may be regarded as about 0.07 mm. long and 0.056 mm. broad, while the villi as 0.27 mm. tall and 0.10 mm. broad. In the sigmoid colon the glands average 0.10 mm. and the villi 0.31 mm. in length.


In the transverse colon of an embryo of 110 mm. (fig. 5), the villi are long and narrow, and give to the colon the appearance of a small intestine of a slightly older embryo. Some of them measure as much as 0.36 to 0.45 mm. in length and average about 0.09 mm. in diameter at their bases. They are covered by a low columnar epithelium (cuboidal in places), which is rather poor in goblet cells. The glands are longer than those of the preceding stage, being about 0.13 to 0.16 mm. in length. The cells which line the glands are distinctly columnar, measuring from 0.022 to 0.028 mm. in height. By far the majority of these are goblet cells. Their nuclei are basally placed and closely crowded together, making this region of the gland very deeply stained.


In the ascending colon, a similar picture is obtained. The villi are, however, somewhat shorter (0.27 to 0.36) mm. Noticeable again is the greater distribution of goblet cells in the glands than on the villi, and the difference in the height of the epithelium in the two regions- In the sigmoid colon and the rectum, the epithelial tube is larger and flattened from side to side. The villi and glands are quite similar as regards size, shape and structure to those in the ascending colon. No epithelial cysts were found in the piece of rectum examined, which was a portion taken rather high up.


In a Well preserved embryo of 120 mm., the transverse colon has a diameter of about 1.08 mm. in contrast to 1.26 mm. in the preceding embryo. The villi, which are closely packed together, are also shorter (0.18 to 0.27 mm.) than those of the former embryo, but the glands are of about the same length. This difference in size is probably due in part to the different preservating fluids used on the two embryos. The epithelium of both villi and glands is in excellent state of preservation and the goblet cells, which have taken the stain (orange—G) very strongly, stand out in marked contrast to the remaining cells. It is easily seen, therefore, that the goblet cells are more nurner— ous on the sides than on the tops of the villi and most numerous in the glands. In many glands these cells appear to be exclusively present. Although the glands are still only short knoblike projections (0.11 to 0.14 mm. in length and 0.09 mm. in width), some of them appear to be double. As will be subsequently described, this bifurcating of the glands is a very important factor in their multiplication.


Conditions in the ascending colon, as regards villi and glands, are similar to those in the transverse. In the rectum the epithelial tube is again flattened laterally measuring 2.12 mm. by 0.69 mm. in cross section. The mucous membrane is thicker (0.32 to 0.36 mm.) than that of the transverse colon (0.27 to 0.32 mm.). Its villi are from 0.22 to 0.27 mm. in height and its glands about the same as those found in the transverse colon (0.13 to 0.16 mm.). Goblet cells are again very numerous. A few epithelial cysts were found in the extreme lower part of the rectum, but these were almost insignificant in size as compared to those of the former stages.

Disappearance of villi

In an embryo of 140 mm. the transverse colon has a diameter of about 1.7 mm. and presents from thirty—siX to forty longitudinal rows of villi. It is apparent, therefore, that the villi are still increasing in numbers as the intestine is increasing in size. Since no distinct longitudinal folds can be found in either models or longitudinal sections, these additional villi must develop from the beginning as separate growths in the spaces between those villi already present. The form of the villi is shown in figure 24. Some of the tallest measure only 0.25 mm. in height. Disregarding the embryo of 120 mm., because of the undoubted shrinkage of all its parts, and referring to the 110 mm. stage, it is seen that the villi are shorter in the older embryo. Moreover, some of the villi are so short at 1-10 mm. that the term villus is scarcely applicable to them, but whether these are newly developed villi or dwindled—down old ones, I am unable to determine. Although the intestinal glands vary in length (0.13 to 0.18 mm.) they are on the whole slightly more advanced than before and many show signs of bilurcating. From the above observations it is evident that, as the glands are increasing in length, the villi are decreasing in height. In the subsequent stages of development, the villi become always lower and lower, so that it is now possible to say that the transitory villi reach their maximum height in embryos between 110 mm. and 140 mm., probably between 110 mm. and 120 mm.


In that portion of the ascending colon adjacent to the colic valve, shorter villi are found (0.14 to 0.18 mm. in height), which are also lower than those in the ileum (0.27 to 0.36 mm.). Higher up in the ascending colon the villi are of about the same size, While the glands are 0.13 to 0.18 mm. in length, and in the beginning of the ascending colon, a few enlarged glands, such as are present in the vermiform process, are found. As regards villi and glands, the descending colon is quite similar to the transverse colon. In the sigmoid colon the villi are longer (0.18 to 0.27 mm.); in the rectum (0.18 to 0.36 mm.). Everywhere, however, the glands remain about the same length as those of the transverse colon. The epithelium is also quite similar throughout the whole colon. It is high columnar in the glands, lower on the sides, and lowest on the apices of the villi. Goblet cells are extremely numerous everywhere, being more abundant in the glands than on the villi.

Effects of distention caused by a storing up of meconium

A marked difference in the thickness of the mucosa is found between the transverse colon of an embryo of 187 mm. and that of the same portion of the intestine of an embryo of 190 mm. (Compare figs. 6 and 7). That of the former is 0.36 mm. in thickness, While that of the latter is only 0.16 to 0.20 mm., the first being about twice the thickness of the second. The question arises, how is this variation to be accounted for? It is to be noted that the portion of intestine of the 190 mm. embryo examined was filled with meconium, thereby extending its Walls and increasing the size of its lumen. The total diameter of its epithelial tube is 4.2 mm., in comparison to 2.3 mm. in the 187 mm. stage. These measurements show only that the epithelial tube is extended in the older stage, but they do not show that the circumference of one is greater in one than in the other, because in the younger stage the epithelial wall is thrown into three or four large folds. In order to determine accurately Whether the folds alone would compensate for so great a difference in diameter, enlarged camera drawings were made, and the length of the lines at the bases of the glands (the line at which the muscularis is just beginning to appear) was measured. The distended gut (190 mm. stage) measured 15.3 mm., while the contracted one only 11.3 mm., showing still a considerable unaccountable differenco. From What I have seen in this and other sections, in the small as WCll as in the large intestine, I have come to the conclusion that Wherever the embryonic intestine is greatly distended with rneconium, is often found to be the case in the older stages, the thickness of the mucosa becomes greatly reduced. In other words, where a considerable amount of meconium is found in the intestine, the thickness of its mucosa varies indirectly with the amount of distension.


Fig. 6 Longitudinal section of the transverse colon of a human embryo of 187 mm. X (50. Shows state of normal contraction (compare villi and glands with those of fig. 7).


Fig. 7 Cross section of the transverse colon of a human embryo of 190 mm. X B0 (compare with fig. (3).


Since the perimeters of the two colons under discussion were unequal in length, it is of interest to compare the number of glands present in them. This was done by counting the number of glands which were practically in contact with the developing muscularis mucosae. This method would not have given comparable results had not the thickness of the sections in both cases been the same (8 microns). In the distended intestine variations from 79 to 96 and an average of 86 were obtained; in the non-distended piece, a variation from 81 to 91 and an average of 85.2, showing that the number of glands is approximately the same. Whether the number of villi around the intestinal wall is the same in both of the intestines, is a harder problem to determine, owing to their greater size and irregularity in height, and to the fact that one is given no distinct basal line, as in the case of the glands, from which to measure. Such a problem could only be determined with any degree of accuracy by making a number of models of comparatively large areas. However, from cross sections alone, it is possible to make out that in the distended intestine the villi are further apart.

In the spreading or stretching out of the mucosa, both the villi and glands become reduced in length. and broadened. The following measurements have been made to show this:

Height of tallest Villi (mm) Width of bases of Villi (mm) Length of Glands (mm) Width of Glands (mm)
Non-distended 0.18-0.27 0.07-0.09 0.22 0.05-0.09
Distended 0.00-0.09 0.14-0.18 0.11-0. 14 0.09-0.14
Reference: Johnson FP. The development of the mucous membrane of the large intestine and vermiform process in the human embryo. (1913) Amer. J Anat., 14: 187-233.

It must be noted that the villi had in many places practically disappeared.

The outer layers of the intestine are also reduced in thickness by distension, a fact which is of common observance in the digestive tube of the adult. In the non-distendecl transverse colon the submucosa, the muscularis, and the serosa together measure about 0.24 mm., the distended one, 0.13 mm.


From the above given figures, the effects of distention, caused by a storing up of meconiuin in the large intestine may be enumerated as follows: (1) an increase in the diameter of the epithelial tube; (2) an increase in the actual surface on which the basal ends of the glands lie’; (3) a decrease in the thickness of the mucous membrane as a whole; (4) a decrease in the length of the glands and an increase in their width ; (5) a more marked decrease in the height of the villi and an increase in their width (6) a spreading apart of the glands and of the villi; and (7) a decrease in thickness in the outer coats of the intestine.


The above results led to the question as to what eifect distention would have upon the intestine of an adult. The small intestine of a guinea—pig was experimentally distended with normal salt solution and fixed and hardened in that condition. Although the results of this and other experiments may be found in the following paper, it may be said here, that the results obtained are largely in accordance with those just described in the rneconium-filled intestine of the human embryo.


Because of the above described effects of marked distention of the large intestine, it has been considered necessary, for the sake of comparison, to select only non—distended portions of the colon for modelling. In the case of the embryo of 190 mm. the sigmoid colon was chosen, for while this region contains meconium, there is no distention. This is made evident by the presence of longitudinal or oblique folds of the mucous membrane, and by the following measurements as compared with those of the transverse colon of the same embryo: diameter of intestine 3.4 mm. ; thickness of mucous membrane 0.34 mm. ,' thickness of outer intestinal coats, 0.23 mm. Figure 22 shows the epithelium of this region of the intestine in surface view. The villi have dwindled down until they appear merely as irregular knobs which are joined together at their bases in the form of ridges. These ridges are of various lengths but all are of about the same thickness. They run in different directions and anastomose with one another, thus marking the surface of the epithelium up into an irregular network such as Langer (’87) has described in connection with the developing colic valve. The clefts in between the ridges are deep, and into them open the lumina of the intestinal glands. An examination of the basal surface of another model (not figured), from the same portion of the large intestine, shows numerous tubular glands, many of which are unbranched, but the branched type is not uncommon.


As stated before, the first beginnings of the intestinal glands appear as small knob-like processes which extend into the underlying mesenchyma. At the time they appear no muscularis Inucosae is present. In embryos of 99 mm., 110 mm., 140 mm., the muscularis mucosae is still not visible ; nevertheless, the intestinal glands all reach a certain depth, so that in a section, a line drawn parallel to the surface of the mucous membrane would practically touch the bottoms of all the glands. It is along this line, or rather, slightly below it, that the muscularis mucosae is becoming visible in an embryo of 187 mm. It is seen as a slight condensation of the mesenchyma forming a circular band of about 0.014 mm. in thickness. In it are observable, though not very distinctly, developing rnyoblasts. The band is slightly more distinct at 190 mm., and separates the connective tissue of the submucosa, which is condensed and well stained, from that of the tunica propria, which is loosely arranged and only faintly or not at all stained. At 187 and 190 mm. the basal ends of the glands can be seen resting upon this layer of muscle.

Further formation of glands

As the glands are gradually increasing in number as the growth of the embryo proceeds, the question arises, how are new glands formed? Do they develop like new villi, by evaginations of the epithelium between those already formed, or are they developed after the manner which Patzelt has described, by a longitudinal splitting of those already present? In his discussion of this point Patzelt says:

"Noch eriibrigt es mir, die Art und Weise anzugeben, wie sich die Lieberki'1hn’schen Driisen verniehren. Bei der Durchsicht dcr Praparate, hauptsaehlieh aus den alteren Stadien, findet man oft im Grunde etwas verbreiterte Driisen. In der Mitte des verbreiterten Grundes erhebt sich ein Epithelhoekerchen. Oft aueh ist dieses Hockerchen nicht mehr blos aus Epithelzellen gebildet, sondern gleicht im Durehsehnitte einem mit Epithcl iiberkleideten Zottchen, welehes in das Innere der Driise hineinragt. Es entspricht dein Durehsehnitte eines kleinen Faltchens, welches den Grund der Druse in zwei Theile spaltet. Dieses Faltchen waehst immer hoher und hoher. Die Druse hat endlich das Aussehen, als ob in einem geineinsanien Vorraum zwei Drusenschlauehe miindeten (Fig. 29 e). Wenn schliesslich die Hohe des Faltchens in gleieher Ebene mit der Innenfléiehe des Darmes steht, ist der Theilungsprocess vollendet, es sind aus einer Driise zwei geworden."

He further believes that the upward growing connective tissue papilla continues its upward growth after it reaches the surface level and thus gives rise to a new villus.

In further support of I’atzelt’s view regarding gland multiplication may be mentioned that if new glands appeared as new outward growths from the epithelium, then one would expect to find always in any fetal intestine glands which extended for varying distances toward the muscularis mucosae. However, such an appearance is never found. The basal ends of the glands, as seen in figures 5, 6, 7, 8, 24 and 25, all extend down to one general level, no intermediate lengths being present. The branched types of glands are always present, some with two, some with three, and some with even four divisions. The amount of bifurcation also varies as Patzelt has figured. As in all problems of growing structures, it is indeed difficult to say precisely what changes are taking place, but I believe it safe to say that in this case that additional glands are developed by a longitudinal splitting of those already present.


In the transverse colon of an embryo of 200 mm. practically the same conditions as those described for the sigmoid colon of the 190 mm. stage are encountered. The mucous membrane, although not thrown up into folds, does not appear stretched out. The villi are of various sizes, the tallest being from 0.14 to 0.18 mm. high. The intestinal glands measure from 0.18 to 0.22 mm. in length. Other measurements taken are as follows:

Diameter of epithelial tube 3.5 mm.

Perimeter, measured at bases of glands 11.1 mm.

Thickness of mucosa 0.40 mm.

Thickness of outer layers .027 mm.

Number of glands touching muscularis mucosae 75.0

Number of glands per running millimeter 6.7

In the iliac colon of the same embryo, a slight distention is present as is indicated by the thickness of both the mucosa (0.32 mm.) and the outer layers (0.18 mm.). Although the preservation of the embryo is poor, enough can be made out from it to see that both villi and glands are shorter and broader than in the transverse colon.


In an embryo of 240 mm. the transverse colon shows some distention, but not so much as was seen in this portion of the large intestine at 190 mm. This is made evident by comparing the thicknesses of the mucosa and the outer coats. As seen in a model (not figured), made at double the magnification of the former model, the mucous membrane presents on its lumen surface a number of large irregular anastomesing folds. Between the folds are clefts, which in some places appear to be the glands themselves; in other places they are merely crypts into which the glands open. The glands are, for the greater part, of the simple tubular type, but some show bifurcations into two or three portions. The epithelium, which varies in thickness from 0.020 to 0.034 mm., is made up of the typical simple columnar cells found in the adult intestine, and contains large numbers of goblet cells. The following list of measurements is given for comparison with the other stages:

Total diameter of epithelial tube 4.6 mm.

Perimeter, measured at the bases of the glands 14.8 mm.

Thickness of mucosa 0.36 mm.

Thickness of outer coats 0.22 mm.

Number of glands touching muscularis mucosae 1140

Number of glands per running millimeter 7.7


In an embryo of 320 mm. a piece of transverse colon which was greatly distended with meconium was examined. The large folds of the mucosa have all disappeared and the intestinal wall as a whole is considerably thinned out. Owing to poor preservation, however, it was not possible to determine the presence of villi and folds. Measurements made are as follows:

Total diameter of epithelial tube 5.5 X 14.5 mm.

Perimeter, measured as before 34.7 mm.

Thickness of mucosa 0.16 mm.

Thickness of outer coats 0.20 mm.

NuIr1l)er of glands 269.0

Number of glands per millimeter 47.7

In a fetus of about seven months (premature birth) the ascending colon seems to be almost entirely devoid of villi and the before-described folds. Although not modelled, it is plain to see that the surface epithelium is for the most part, though not entirely, level. At more or less regular intervals, it dips down into the cylindrical intestinal glands. Measurements:

Total diameter of epithelial 3.7 mm.

Perimeter 8.5 mm.

Thickness of mucosa 0.27 mm.

Thickness of outer coats 0.54 mm.

Number of glands 162.0

Number of glands per millimeter 8.’?

Sections of the sigmoid colon show a similar condition as regards glands. They are of an equal length and similarly distributed.


Fig. 8 Cross section of the mucosa of the transverse colon of a human embryo at birth. X 60.


In a fully developed fetus at birth (fig. 8), a condition is reached in which the villi have entirely disappeared. A model of a portion of the epithelium of the transverse colon is shown in figure 25. As seen from the model, only glands are present, the openings of which appear irregular when viewed from the lumen side. For the most part the mouths of the glands open singly to the surface, but in one region of the model, three can be seen opening together in a slightly depressed region of the surface epithelium. The glands are still of the simple and bifurcated types, the bifurcated cries representing different stages in the process of splitting. The epithelium, which is similar to that in the adult, is 0.017 mm. in thickness at the surface, while in the glands it measures 0.28 mm. Goblet cells are still numerous. Measurements made from cross sections of the transverse colon at birth are as follows:

Diameter of epithelial tube 5.5 mm.

Perimeter 39.0 mm.

’l‘hic-liness of mucosa 0.25 mm.

Thickness of outer coats 0.27-0.72 mm.

Number of glands 3840

Number of glands per millimeter 9.8

Summary

To the foregoing observations the following summary may be added. As has been pointed out before, the cylindrical tube of epithelium of the early stages develops longitudinal thickenings or ridges. In an embryo of 58 mm. these are becoming partially transformed into low longitudinal folds. In embryos of 65 mm. these folds apparently segment, and in embryos of 88 to 99 mm. true villi are present. We have, therefore, longitudinal folds apparently subdivided to form villi. This view concerning the formation of the villi in the small intestine has been presented by Berry (’00) and confirmed by Forssner (’07). In opposition to this, the view that the villi arise as separate growths of the epithelium, not preceded by folds, has been maintained by Koelliker (’61 and ’79), Barth C68), and Brand (’77). Voigt C09) believed that the surface epithelium was cut up into a number of elevations by a net Work of fissures and furrows, and that these elevations grew into villi. In a study of the development of the Whole of the human small intestine the present author (’10) Wrote:

In briefly summarizing the development of villi, it may be said that the general tendency throughout the whole of the small intestine is for villi to develop as separate invaginations of the epithelium. Owing however, to the occurrence of transitory structures (vacuoles, diverticula, and folds) their development is manifested differently in different parts of the intestine.


Although in the large intestine formation of villi is preceded by distinct longitudinal folds, it does not seem probable to me, after a study of my models, that there is a mechanical segmentation of the longitudinal folds. It must be remembered that the epithelial tube is ever growing by an increase in the number of its cells, and by the enlargement and duplication of its parts. Because of this active growth one would expect, therefore, villi to form by an active direct process, rather than by an indirect one. It seems more probable to me, that small knob—like elevations are developed along the tops of the folds, and that these knobs form into villi. If such were the case, the picture presented would always be one which would appear like a segmen— tation of folds. As the villi grew taller and taller, the segmenting fissures would appear to be sinking in deeper and deeper. It is important in this connection to note that the original folds are considerably smaller than the villi, a fact which is in favor of the view just proposed. Regarding the further development of villi, it may be said with certainty, that they arise separately in between those already present.


The earliest glands develop as small knob—like growths of the epithelium into the mesenchyma. As has been pointed out before, the additional glands are probably formed by a longitudinal splitting of those already present.

The villi reach their maximum height in embryos of 110 mm. to 140 mm. in length. From this stage on they gradually become smaller and smaller. A fusion of adjacent villi together at their bases, which gradually extends towards their apices and lengthens the intestinal glands, has been described by Koelliker (’61) and Schultze (’99) as the manner in which they disappear. Brand (’77) describes the connective tissue about the glands as the active factor in their disappearance. He believes that the connective tissue gradually grows higher and higher, and in so doing, moulds the epithelium of the villi into that of the glands. Schirman (’98) describes the disappearance of the villi of the large intestine of the guinea-pig in an entirely different manner as follows:

Die cmbryonalen Zotten des Dickdarms bestehen beim l\/leerschweinchen zu vier Funfteln ihrcr Liinge einzig aus Epithelzellen, nur das basale Fiinftcl der Zotte cnthalt einen axialen, Blutgefasse fi‘1hrenden Bindegcwebstrang. Nur dieses basale Funftel bleibt erhalten und geht in dcr Bildung der Lieberk1'ihn’schen Driisen auf, der grossere Rest Wird zuruckgebildet-, er zerfallt.

It is certain that no such process as Schirman has described takes place in the human large intestine.

The disappearance of villi is indeed diflicult to explain in mechanical terms. All that can be said with certainty is that the villi gradually develop, reach a certain maximum height, and then gradually fade out. It is of interest in this connection, however, to note that the effect of distention of the large intestine, caused by a storing up of meconium, brings about a disappearance, or at least a partial disappearance, of the villi. It is hardly probable that mechanical distention of this kind is connected with a lasting disappearance of villi of the large intestine, for they do not disappear permanently from the small intestine, where distentions are also found.

Develnpmemf of the plicae semilunares coli

The before described longitudinal and oblique folds of the epithelium of the colon are in no Way related to the later plica.e semilunares. They disappear with the development of villi, and therefore, are only transient structures. The larger plicae se1ni— lunares are of later origin, and as they run an oblique course along the Wall of the intestine, they have been studied from both cross and longitudinal sections. The observations shown in table 1, have been made to indicate the condition of the inner surface of the large intestine as regards these folds.

Table 1 Showing the development of the plicae semularis
Embryo (mm) Ascending Colon Transverse Colon Descending Colon Iliac Colon
65 2 large longitudinal folds 3 large longitudinal folds None
65 2 large and 1 small longit. fold 2-3 very low None None small longit. folds fold
70 1-2 large folds somewhat oblique folds 1 low broad fold
88 3 distinct longit folds 2-3 longit. folds Very low, but folds broad circ. folds, 0.09 to 0.13 mm. high
99 1-2 longit. folds
110 Slight indication of folds Slight indication of folds
120 None None None None
140 Oblique folds, 0.09 mm high, 0.90 mm broad, 0.07 - 0.14 mm apart
190 None (intestine distended) Oblique folds, 0.18-0.45 mm high, 0.27-0.36 mm broad, 1.0 - 1.6 mm apart
240 Oblique fold s, 0.09-0.27 mm. high, 0.36-0.90 In m. b r 0 a. d, 1 .2 — 1 .6 In In. apart.
320 None (intestine distended)
7 months fetus Oblique folds foetus 0.36-0.54 mm. high, 0.36 mm broad, 0.7-1.3 mm apart. Oblique folds similar to those in ascending colon.
Birth Oblique folds, 0.09 mm. high, 0.36 - 0.45 mm broad, 1.3-1.4 mm apart Oblique folds 1.3 - 3.0 mm high, 0.36-0.54 mm. broad. mm (seen in cross sections only) Slight indication of Oblique folds
Reference: Johnson FP. The development of the mucous membrane of the large intestine and vermiform process in the human embryo. (1913) Amer. J Anat., 14: 187-233.


From table 1 it would appear that the earlier longitudinal folds which develop before the 120 mm. stage are lost. Later oblique folds are formed which, owing to their course, position, and constancy, must be the plicae scmilunares coli. These folds, however, are not present in portions of the large intestine which are distended, although the opposite View is held by some regarding those of the adult.

The Vermiform Process

Early development

The history of the mucosa of the vermiform process in the human embryo is quite similar to that of the colon. One finds first an epithelial tube with smooth walls and a round lumen. Later as the tube grows in size, folds appear. The folds give place to villi and glands develop. VVith the development of glands the villi disappear. Unlike the glands of the colon, however, those of the vermiform process oftentimes develop into cysts, which degenerate, and thus cause a decrease in the number of glands. In the following brief description, numerous references are made to the already described conditions of the large intestine.


The early development of the vermiform process has been described in connection with the early stages of the colon. In the last—described stage (42 mm.) it is a simple tube of epithelium of about two to four cell nuclei in thickness, and presents on its inner surface three or four slight ridges. At 55 mm. the epithelial tube is decidedly large near its base (0.60 mm.), but rapidly becomes smaller when followed towards its tip. The epithelium of the basal portion is thrown into ridges which resemble very much those of the ascending colon of the same embryo. A few vacuoles are present in some of the higher ridges. In the base of the vermiform process of an embryo of 58 mm. (diameter only 0.40 mm.) the epithelial ridges are more numerous They continue distalward for a short distance and gradually fade out.


At 65 mm. the base of the vermiform process measures 0.45 to 0.54 mm. in diameter. Its epithelium is now provided with distinct villi which resemble those found in the ileum and ascending colon of the same stage. Followed distalward the vermiform process becomes somewhat smaller, but even to its end, villi are present. In some places they appear to be forming from longitudinal folds. The epithelium is everywhere simple columnar and has a thickness ranging from 0.028 to 0.042 mm. in thickness, depending whether measured on tops of the folds or between them. The large number of goblet cells present is striking, there being by far a greater number in the vermiform process than in the small or large intestine.


In an embryo of 88 mm. the diameter of the vermiform process at its base is about 0.45 mm. Numerous villi of about the same size as those in the lower part of the ileum at this stage (0.25 to 0.27 mm. in height) are found. The glands have begun to appear and in places Where they are cut in cross section they show small round lumina. Toward its tip the villi are distinct, but shorter (0.11 mm. high). Some are in the form of longitudinal folds (fig. 26). Glands are in most places very small, but their beginnings are everywhere visible.


The epithelial tube of the base of the vermiform process in an embryo of 110 mm. has a diameter of about 0.70 mm. Both glands and villi are distinct, but the former are as yet very rudimentary. In most places they are, as well as can be determined from cross and longitudinal sections, 0.09 to 0.11 mm. in length. The villi are shorter than those found in the base of the Vermiform process of the preceding stage, being only 0.14 to 0.16 mm. in height. Goblet cells are again very numerous. The distal end has a diameter of 0.77 mm., being slightly greater than its proximal portion. The villi are again shorter (0.11 to 0.13 mm.) than those found above, but somewhat longer than those found in the same portion of the vermiform process of the preceding embryo. The glands are approximately the same length as before. The extreme tip is rounded in shape, and is provided with villi and glands of the same type as those on the side walls. 220 FRANKLIN PARADISE JOHNSON

Enlarged glands and gland cysts

In an embryo of 140 mm. the epithelial tube of tlie caecum is 1.4 mm. in diameter, and its villi 0.18 mm. to 0.27 mm. high. For the most part the glands are 0.09 to 0.13 mm. in length and 0.054 to 0.072 mm. in width. Some of the glands, however, are swollen at their lower ends, being from 0.09 mm. to 0.13 mm. in diameter. They are all supplied with lumina, which in the enlarged glands are occluded at the necks of the glands. More distally, the base of the vermiform process has a diameter of only 0.9 mm. The villi are similar to those of the caecum, and the bulbous glands are more numerous. Still more distally, near the tip of the vermiform process, the villi are shorter (0.14 to 0.16 mm.), and the enlarged glands are found in still greater numbers. Figure 27, from a model of the epithelium of the tip shows some of these glands. Many have enlarged ends connected with the surface epithelium by constricted necks. The gland marked in the figure is the only gland which could be found which is entirely cut off from the surface epithelium. From serial sections, it is possible to make out that although the bulb-like expansions are provided with decidedly large lumina, these are totally out off from the lumen of the vcrmiform process. Moreover, the cells of the necks of the glands appear to be undergoing degenerative changes. In many places only a slight strand of tissue, largely composed of epithelial cell nuclei, could be found connecting the bulb with the surface epithelium.


In the vermiform process of an embryo of 170 mm. the enlarged glands are very numerous. Owing, however, to poor preservation it is impossible to state whether they are connected with the surface or not. In the connective tissue of the submucosa can now be seen distinct nodules of lymphoid tissue.


Sections through the base of the Vermiform process of an embryo of 190 mm. shows ill-marked villi, 0.07 to 0.11 mm. in height and of variable width. The glands, now 0.11 mm. to 0.16 mm. long, are more regular and only a few tend to be bulbous. The condition found is quite similar to that of the sigmoid colon of the same embryo with the difference that there are fewer glands present. For the first time, the muscularis mucosae becomes Visible, arid the glands in places pierce it. In the tip of the vermiform process the epithelial tube is expanded to a diameter of 1.7 mm., in comparison to 0.6 mm. at its base. The villi have practically disappeared, only very slight elevations being left in places. The glands are similar in form, but farther apart than those of the base. In places the muscularis mucosae can be seen, but it is not well differentiated as yet.


In an embryo of 200 mm. the epithelial tube of the base of the vermiferm process (fig. 28), although its diameter is about the same (1.6 mm.), is quite different from that of the preceding stage. The villi have almost everywhere entirely disappeared. The glands are of Various size, some of the swollen ones being 0.13 to 0.14 mm. broad. Most of these extend down only to the muscularis mucosae, others have pushed into it and cause it to bulge outward, while still others have pierced it. In some places the swollen ends of glands appear as cysts, entirely out off from the surface epithelium (figs. 10 and 2-8). Some cysts appear to be entirely surrounded by a thin stratum of smooth muscle derived from the museularis mucosae. The epithelium li11ing the cysts shows various stages of degeneration. In some it appears almost similar to the surface epithelium. In others only that part of the epithelium lining the base of the cyst is similar to that of the surface, while the upper portion, that is, that portion of the cyst which had formerly been the neck of the gland, has an epithelium which is much thinner and co111— posed largely of broken dow11 nuclei and fragments of cell protoplasm. In other cysts, degeneration has involved all the cells of the epithelium, but those in the upper end again show a more advanced stage of deterioration. Still other cysts are of smaller size and have their epithelia reduced to a thin line.


Stohr C98) and Nagy (’11) found epithelial cysts of the kind described in the vermiform process of human embryos. According to Stohr the epithelium of the cut off glands becomes poorer and poorer in goblet cells and begins to degenerate. The cyst itself becomes filled with degenerative products, and as the epithelium gradually goes to pieces the walls collapse. He concludes: “Als letzten Rest der Druse findet man dann minimale, ().()5—0.15 mm. messende Gruppen kleiner Epithelzellen, die VOI1 einer dicken bindegewebigen Kapsel (Fig. 19a) umgeben sind.”


Figs. 9 and 10 Cross sections of the Inueosa of the vermiform process (including the circular layer of the muscula.ri.s). Human embryo of 200 mm. X 120. In figure 19 is shown at gland cyst not entirely out off from the surface epithelium. In figure 10 is shown a cyst detached from the surface epithelium and undergoing degenerative changes.

Fig. 11 Mucosa of the rectum (including the circular layer of the muscularis) in cross section. Human embryo of 65 mm. X 120. Shows several epithelial gland cysts.


Numerous and distinct lymphoid nodules are present in the vermiform processes of all the embryos from 170 mm. up, but never, so far as I have observed, are the cysts located in them. I agree with Stéihr when he says: “Der Verfolg der Serie zeigt immer, dass die reducirten Driisen nur am Rande des Knotchens liegen, zuweilen sogar in dessen Peripherie hineingepresst sind. Das Centrum der Knotchen enthalt keine reducirten Driisen.”


Moreover, such a degeneration of glands is not found in other portions of the large intestine where lymphoid nodules are plentiful. It is not probable, therefore, that the development of lymphoid tissue has anything to do with the formation and degeneration of these cysts.


There are no marked changes in the form of the mucosa of the Vermiform process in the subsequent stages of development. At 240 mm. villi, bulbous glands, and cysts have entirely disappeared. The glands, as seen in figure 29, are small and rather Widely separated. The muscularis rnueosae is distinct and oceasionally glands can be seen which have pierced it.


In specimens at seven months, birth, and a two Weeks old child, practically the same conditions are found. Lymphoid tissue, both in the diffuse and nodular form, is abundant. The statement made by Berry and Lack (’06) that “In the vermiform appendix of the full term feotus there is practically no lymphoid tissue, or at least so little as to constitute a negligible quantity, Whilst lymphoid follicles are absent,” cannot be confirmed.

Crown-Rump Length (mm) Diameter of epithelial tube Perimeter, measured at bases of glands Thickness of mucosa Thickness of outer layers Number of glands touching muscularis mucosae Number of glands per running millimeter
200 3.5 mm. 11.1 mm. 0.40 mm. 0.27 mm. 75.0 6.7

Fetus 200 mm

In the transverse colon of an embryo of 200 mm. practically the same conditions as those described for the sigmoid colon of the 190 mm. stage are encountered. The mucous membrane, although not thrown up into folds, does not appear stretched out. The villi are of various sizes, the tallest being from 0.14 to 0.18 mm. high. The intestinal glands measure from 0.18 to 0.22 mm. in length. Other measurements taken are as follows:

Diameter of epithelial tube 3.5 mm.

Perimeter, measured at bases of glands 11.1 mm.

Thickness of mucosa 0.40 mm.

Thickness of outer layers .027 mm.

Number of glands touching muscularis mucosae 75.0

Number of glands per running millimeter 6.7

Fetus 240 mm

In an embryo of 240 mm. the transverse colon shows some distention, but not so much as was seen in this portion of the large intestine at 190 mm. This is made evident by comparing the thicknesses of the mucosa and the outer coats. As seen in a model (not figured), made at double the magnification of the former model, the mucous membrane presents on its lumen surface a number of large irregular anastomesing folds. Between the folds are clefts, which in some places appear to be the glands themselves; in other places they are merely crypts into which the glands open. The glands are, for the greater part, of the simple tubular type, but some show bifurcations into two or three portions. The epithelium, which varies in thickness from 0.020 to 0.034 mm., is made up of the typical simple columnar cells found in the adult intestine, and contains large numbers of goblet cells. The following list of measurements is given for comparison with the other stages:

Total diameter of epithelial tube 4.6 mm.

Perimeter, measured at the bases of the glands 14.8 mm.

Thickness of mucosa 0.36 mm.

Thickness of outer coats 0.22 mm.

Number of glands touching muscularis mucosae 1140

Number of glands per running millimeter 7.7

Fetus 320 mm

In an embryo of 320 mm. a piece of transverse colon which was greatly distended with meconium was examined. The large folds of the mucosa have all disappeared and the intestinal wall as a whole is considerably thinned out. Owing to poor preservation, however, it was not possible to determine the presence of villi and folds. Measurements made are as follows:

Total diameter of epithelial tube 5.5 X 14.5 mm.

Perimeter, measured as before 34.7 mm.

Thickness of mucosa 0.16 mm.

Thickness of outer coats 0.20 mm.

NuIr1l)er of glands 269.0

Number of glands per millimeter 47.7


Fetus 7 months

In a fetus of about seven months (premature birth) the ascending colon seems to be almost entirely devoid of villi and the before-described folds. Although not modelled, it is plain to see that the surface epithelium is for the most part, though not entirely, level. At more or less regular intervals, it dips down into the cylindrical intestinal glands. Measurements:

Total diameter of epithelial 3.7 mm.

Perimeter 8.5 mm.

Thickness of mucosa 0.27 mm.

Thickness of outer coats 0.54 mm.

Number of glands 162.0

Number of glands per millimeter 8.’?

Sections of the sigmoid colon show a similar condition as regards glands. They are of an equal length and similarly distributed.

Birth

In a fully developed fetus at birth (fig. 8), a condition is reached in which the villi have entirely disappeared. A model of a portion of the epithelium of the transverse colon is shown in figure 25. As seen from the model, only glands are present, the openings of which appear irregular when viewed from the lumen side. For the most part the mouths of the glands open singly to the surface, but in one region of the model, three can be seen opening together in a slightly depressed region of the surface epithelium. The glands are still of the simple and bifurcated types, the bifurcated cries representing different stages in the process of splitting. The epithelium, which is similar to that in the adult, is 0.017 mm. in thickness at the surface, while in the glands it measures 0.28 mm. Goblet cells are still numerous. Measurements made from cross sections of the transverse colon at birth are as follows:

Diameter of epithelial tube 5.5 mm.

Perimeter 39.0 mm.

’l‘hic-liness of mucosa 0.25 mm.

Thickness of outer coats 0.27-0.72 mm.

Number of glands 3840

Number of glands per millimeter 9.8

Conclusions

  1. The large intestine, like the oesophagus, stomach, and small intestine, is at first a simple tube of epithelium, and is the last portion of the digestive tube to show distinctive changes in the form of its mucosa. The first change which occurs is the formation of longitudinal folds and ridges.
  2. The ridges and folds first appear in the rectum and then extend upward (orally). A second point of growth is found in the ascending colon at the colic valve. The direction of growth here is in the opposite direction (aborally). The transverse colon is the last portion of the large intestine to develop ridges and folds.
  3. A few vacuoles similar to those found in the oesophagus, stomach, and small intestine, are found in the epithelial wall of the large intestine in its early stages.
  4. The longitudinal folds are replaced by Villi in a manner which suggests a segmenting of folds. However, it is not improbable that the villi of the large intestine arise after the manner of those of the small intestine, as separate growths along the tops of the folds.
  5. Additional villi arise as separate growths between those Villi already formed, not being preceded by folds.
  6. The first glands appear as knob—like protuberances of the epithelium into the underlying mesenchyma. Additional glands develop by a splitting, from below upwards, of those already formed.
  7. Villi reach their maximum height in embryos between 110 mm. and 140 mm. in length. From this time on they gradually become smaller in size. Remnants of them persist as folds which form an irregular network in between the gland openings. They are entirely’ gone at birth.
  8. In the vermiform process villi and glands develop, and the villi disappear at the same time and in the same manner as those of the ascending colon.
  9. Enlarged and cystic glands are found in the Veriniform process and eaecum. Many of them become detached from the surface epithelium and are then entirely surrounded by connective tissue. They later disappear by degeneration and absorption. Lymphoid nodules are found in abundance in the vermi form process at birth, but the cysts never lie in the centers of them.
  10. Epithelial cysts are also found in the mucosa of the rectum. They are in many Ways similar to those found in the vermiform process, but differ from them in that they are not so deeply seated in the tuniea propria, are seldom entirely detached from the surface epithelium, and disappear not by degeneration and absorption, but by breaking through into the intestinal lumen.
  11. Distention of the large intestine, due to the accumulation of meconium, brings about marked changes in the form of the mucosa. It reduces its thickness, broadens and shortens both villi and glands, and causes them to become spread apart.

Bibliography

B.-‘:.(}INb‘KY, A. 1882 Un{.ersuch1u1gen fiber den Darmkanal dos mensehlichen Kindes. Arch. F. path. Anat., Bd. 89, pp. fi4—94.

BARTH 1868 Beitrage zur Iflntwickelung der Darmwand. Sitzungsb. d. Wien. Akad. d. Wissensch., Bd. 58, pp. 128436.

BERRY, J. M. 1900 On the development of villi in the human intestine. Anat. Anz., Bd. 17, pp. 242-249.

BERRY, R. J. A., AND LACK, L. A. H. 1906 The vermiform appendix of man, and the structural changes therein coincident with age. Jour. Anat. Physiol., vol. 40, pp. 2417-256.

BRAND, E. 1877 Beitréige zur Entwiekelung der Magen— und Darmwand. Verhandl. d. phys. -med. Gesellsch. zu Wi11‘zb., Bd. 9, pp. 243—256.

Johnson FP. The development of the mucous membrane of the oesophagus, stomach and small intestine in the human embryo. (1910) Amer. J Anat., 10: 521-559.

JoHNsoN, F. P. 1910 The development of the mucous membrane of the oesophagus, stomach, and small intestine in the human embryo. Am. Jour. Anat., vol. 10, pp. 521-561.

KOELLIKER, A. 1861 Entwiekelungsgeschiehte des Menschen und der hoheren 'I‘hiere. Leipzig.

1879 lbid. 2e Aufi.

LANGER, C. Von 1887 Ueber das Verh.-«1ltcn der Darmschleinihaut an de1' 1liocoecal-Klappe, nebst Bemerkungen fiber ihre Entwieklung. Denkschriften d. k. Akad. d. W. math.—natur\v. Classe, Bd. 54, Abt. 1, pp. 51-58.

LEWIS, F. T. 1911 Die Entwicklung (les Di<:kd:u'1ns. Handbllch der EntWiclzliingsgeschichte des Mensclien, herausgegeben Von Keibel und Mall. Rd. 2, siebzehntes T\"apitel, pp. 3824391. 226 FRANKLIN PARADISE JOHNSON

NAGY, L. V. 1911 Ueber die Histogenese des Darmkanals bci menschlichen Embryonen. Anat. Anz., Bd. 40, pp. l47~156. PATZELT, V. 1883 Ueber die Entwicklung der Diek(la.rIr1schleimhaut. Sitzungsb. d. k. Akad. d. Wissensch. Wien. Bd. 86, pp. 145472. SCHIRMAN, D. 1898 Ueber die Rtickbildung der Diekdarmzotten des Meerschweinchens. Verhandl. cl. phys.-med. Gesellsch. z. Wi1rzb., N.F., Bd. 32, pp. 1~9.

SCHULTZE, O. 1899 Grundriss der Entwickclungsgeschichte des Menschen und der Séiugethiere. Leipzig.

STo'HP., P. 1898 Uebcr die Entwicklung der Darmlymphknotchen und fiber die Riiclzbildung VOH Darmdrusen. Arch. f. mikr. Anat., Bd. 51, pp. 1—55.

VOIGT, J. 1899 Beitrag zur Entwickelung dcr Darmselileimhaut. Anat. Hefte, Abt. 1, Bd. 12, pp. 4940.

Plates

Plate 1

12 Wax reconstruction of the epithelium of the ascending colon. Human embryo of 50 mm. X89.

13 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 50 mm. X 89.

14 Wax reconstruction of the epithelium of the descending colon. Human embryo of 50 mm. X 89.

15 Wax reconstruction of the epithelium of the ascending colon (portion near the colic valve). Human embryo of 58 mm. X 89.

16 Wax reconstruction of same. More caudad portion. X 89.

17 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 58 mm. X 89.

18 Wax reconstruction of the epithelium of the descending colon. Human embryo of 58 mm. X 89.

Plate 2

19 Wax reconstruction of the epithelium of the upper part of the rectum. Human embryo of 58 mm. X 89; ac, epithelial gland cyst.

20 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 65 mm. X 89.

21 V5/ax reconstruction of the epithelium of the descending colon. Iluman embryo of 65 mm. X 89.

22 Wax reconstruction of the epithelium of the sigmoid colon. Human em~ lbryo of 190 mm. X 89.

Plate 3

23 Wax reconstrmtinn of the epithelium of the transverse colon. Human embryo of 99 mm. X 89.

24 Wax reconstruction of the epithelium of the transverse colon. Human embryo of 140 mm. X 89.

25 Wax reconstruction of the epithelium of the transverse colon. Human embryo at birth. X 178.


Plate 4

26 Wax reconstruction of the epithelium of the tip of the vermiform process. Human embryo of 88 mm. X 89.

27 Wax reconstruction of the epitheliuni of the tip of the vcrmiform process‘ Human embryo of 140 mm. X 89; :1}, epithelial gland cyst, entirely out ofi from surface epithelium.

28 Wax reeonstructioii of the epithelium of the base of the vermiform process. Human embryo of 200 mm. X 89; 3:, epithelial gland cyst, entirely out off.

29 Wax reconstruction of the epithelium of the tip of the vermiform process. Human embryo of 240 mm. X 89.

Cite this page: Hill, M.A. (2024, May 23) Embryology Paper - The development of the mucous membrane of the large intestine and vermiform process in the human embryo. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Paper_-_The_development_of_the_mucous_membrane_of_the_large_intestine_and_vermiform_process_in_the_human_embryo

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