The embryology of gut rotation.
ABSTRACT Until today, the puzzling spectrum of midgut "malrotations" is commonly explained by an "impaired" process of rotation of the midgut. However, a closer look at the literature reveals that the description of this "process of rotation" is rather schematic and is aimed more at explaining pathological findings, while detailed proper embryological investigations are still rare. Despite recent trials, good animals models that would allow the comparison of normal and abnormal midgut development are still missing. In the first part of this article, the "normal process of rotation," as it is described in the literature, is presented and critically analyzed. In general, it is a shortcoming that reliable illustrations of these crucial embryological processes are missing in most of these papers. Therefore, in the second part of this review scanning electron microscopy pictures of the developing midgut are presented in a series of rat embryos. In these pictures clear signs of a process of rotation are missing.
- SourceAvailable from: onlinelibrary.wiley.com[Show abstract] [Hide abstract]
ABSTRACT: During digestive organogenesis, the primitive gut tube (PGT) undergoes dramatic elongation and forms a lumen lined by a single-layer of epithelium. In Xenopus, endoderm cells in the core of the PGT rearrange during gut elongation, but the morphogenetic mechanisms controlling their reorganization are undetermined. Here, we define the dynamic changes in endoderm cell shape, polarity, and tissue architecture that underlie Xenopus gut morphogenesis. Gut endoderm cells intercalate radially, between their anterior and posterior neighbors, transforming the nearly solid endoderm core into a single layer of epithelium while concomitantly eliciting "radially convergent" extension within the gut walls. Inhibition of Rho/ROCK/Myosin II activity prevents endoderm rearrangements and consequently perturbs both gut elongation and digestive epithelial morphogenesis. Our results suggest that the cellular and molecular events driving tissue elongation in the PGT are mechanistically analogous to those that function during gastrulation, but occur within a novel cylindrical geometry to generate an epithelial-lined tube.Developmental Dynamics 11/2009; 238(12):3111-25. · 2.59 Impact Factor
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ABSTRACT: The ability to generate conditional mutant alleles in mice using Cre-lox technology has facilitated analysis of genes playing critical roles in multiple developmental processes at different times. We used a transgenic Hoxb6 promoter to drive tamoxifen-dependent Cre recombinase expression in several developing systems that serve as major models for elucidating inductive interactions and mechanisms of morphogenesis, including lateral plate mesoderm and descendant limb buds, neural crest progenitors of the neural tube, tailbud, and CNS isthmic organizer. The Hoxb6CreER(T) line gives very rapid and complete recombination over a short time window after a single tamoxifen dose, allowing precise time requirements for gene function to be assessed accurately. Embryonic cells cultured from the Hoxb6CreER(T) line also display rapid recombination ex vivo after tamoxifen exposure. Hence, the Hoxb6CreER(T) line provides a valuable tool for analyzing gene function, as well as lineage tracing studies using genetic cell marking, in several developing systems.Developmental Dynamics 02/2009; 238(2):467-74. · 2.59 Impact Factor
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ABSTRACT: Right paraduodenal hernia (PDH) results from a primitive gut malrotation. The resultant jejunal mesenteric defect posterior to the superior mesenteric vessels allows decompressed jejunum to herniate retroperitoneally. PDH make up 53% of all internal hernias, but account for only 0.2% to 5.8% of all cases of intestinal obstruction. In addition, PDH exhibits male and left-sided predominance. Ours is the second report to describe the preoperative diagnosis and totally laparoscopic repair of a right PDH. We report the case of a 26-year-old female with symptoms suggestive of partial small bowel obstruction and a 6-year history of intermittent abdominal pain. Physical examination demonstrated lower quadrant tenderness. Plain abdominal radiographs and ultrasonography were nondiagnostic. Contrasted computed tomography of the abdomen revealed jejunum encased within the right upper quadrant suspicious for right PDH. The patient underwent successful laparoscopic right PDH repair and was discharged home on postoperative day 1 without late sequelae. In the outpatient setting, clinical suspicion and comprehensive radiological investigation permit preoperative diagnosis of right PDH. In acute situations, clinical presentation, plain radiographs, and then diagnostic laparoscopy may be an expeditious diagnostic algorithm. Subsequent laparoscopic repair of right PDH is feasible and may shorten hospital length of stay.JSLS: Journal of the Society of Laparoendoscopic Surgeons / Society of Laparoendoscopic Surgeons 01/2009; 13(2):242-9. · 0.81 Impact Factor
The Embryology of Gut Rotation
By D. Kluth, S. Jaeschke-Melli, and H. Fiegel
Until today, the puzzling spectrum of midgut “malrotations” is
commonly explained by an “impaired” process of rotation of
the midgut. However, a closer look at the literature reveals
that the description of this “process of rotation” is rather
schematic and is aimed more at explaining pathological find-
ings, while detailed proper embryological investigations are
still rare. Despite recent trials, good animals models that
would allow the comparison of normal and abnormal midgut
ing that reliable illustrations of these crucial embryological
processes are missing in most of these papers. Therefore, in
the second part of this review scanning electron microscopy
pictures of the developing midgut are presented in a series of
rat embryos. In these pictures clear signs of a process of rota-
tion are missing.
© 2003 Elsevier Inc. All rights reserved.
of the gut inside the abdominal cavity results after a
complex embryological process called “rotation of the
midgut loop.” Consequently, disorders of the positioning
of the gut are called “malrotation.”1,3-5However, in most
textbooks of embryology and pediatric surgery, this pro-
cess of rotation is described rather schematically. In-
structive illustrations representing results of detailed em-
bryological studies of midgut development are sparse.
Animal models, which may allow embryological studies
in specimen with “malrotations” of the midgut, have
recently been discussed but are still controversial.6,7
In this review, the embryology of the midgut will be
discussed in two sections:
1. The description of “normal midgut development”
as it can be found in most textbooks of embryology
and pediatric surgery.
2. An “atlas of midgut development” using scanning
electron photographs. These pictures give an impres-
INCE THE WORK of Mall1and Frazer and Rob-
bins,2it is generally believed that the normal position
“NORMAL” EMBRYOLOGY OF THE MIDGUT
The normal embryology of the midgut is described as
it is found in most papers and textbooks of embryology8,9
and pediatric surgery.4,10,11
In humans, the development of the midgut starts with
the subdivision of the primitive gut into foregut, midgut,
and hindgut at the fourth developmental week.8,9At this
stage, the midgut is still connected to the yolk sac
through the omphaloenteric duct. Many researchers be-
lieve that the midgut lies straight in the midline of the
embryo in this stage.
The Process of Rotation
This process can be subdivided into two or three
subsequent developmental steps.3,8,9
1. The early development of the gut anlage into the
extraembryonic coelom with a sagittal orientation
of the primitive loop (approx. fourth week of de-
velopment in humans). Many researchers believe
that this herniation (physiological umbilical hernia)
results because the gut grows too fast in relation to
the abdominal cavity of the embryo.3In this stage,
the first rotation of the gut anlage inside the ex-
traembryonic coelom takes place. It is 90° in a
counterclockwise direction around the axis of the
mesentery vessels (approx. eighth week of devel-
opment in humans). As a result, the midgut loop is
now horizontally orientated with the small gut to
the right and the colorectum to the left.
2. “Return of the gut” into the abdominal cavity (ap-
prox. tenth week of development in humans).
At the tenth week of development, the extraembryonic
part of the gut enters the abdominal cavity. The details of
this process are still unclear. Some authors believe that
the process of rotation ends at this stage with another
rotation in an anticlockwise fashion (180°).11As a result,
the flexura duodeni is pushed into a position below and
to the left of the root of the mesentery while the cecum
and the colon are forced to the right side of the abdom-
inal cavity, thus crossing over the mesenteric root.
The end result of these two rotations is a complete
rotation of 270°. In the following step, the cecum grows
downwards from the upper quadrant of the right abdom-
inal cavity into the right iliac fossa.
In contrast to this description, Grob3subdivides the
last rotation of 180° into two steps of 90° each.
1. This description of this process of rotation is sche-
matic. Good illustrations of important developmen-
tal steps are rare. The reason is that most descrip-
tions of the embryology of the midgut were done in
order to better explain the background of the pa-
From the Department of Pediatric Surgery, University Hospital
Eppendorf, Hamburg, Germany.
Address reprint requests to Professor Dietrich Kluth, MD, PhD,
Department of Pediatric Surgery, University Hospital Hamburg Ep-
pendorf, Martinistr. 52, 20246 Hamburg, Germany.
© 2003 Elsevier Inc. All rights reserved.
275 Seminars in Pediatric Surgery, Vol 12, No 4 (November), 2003: pp 275-279
thology of malrotation than to explain the embry-
ology of the midgut.
2. Many clinicians as well as embryologists believe
that congenital malformations in general are best
explained by a process of inhibition of normal
embryonic development. The theory of rotation of
the midgut is a good example for this assumption.
Most workers in the field believe that this process
of rotation can be hampered at any stage resulting
in the known spectrum of malrotations. It is a
shortcoming of this theory, however, that these
“normal forms” of rotation only exist in schematic
drawings. They have never been demonstrated in
3. Furthermore, it is another popular assumption that
the morphology of normal embryological stages
can be mimicked by the morphology of patholog-
ical conditions,12indicating that that malformations
represent “frozen” stages of normal embryos. As a
result, the understanding of the development of the
intraabdominal position of the gut is highly hypo-
thetical: they represent interesting interpretations of
pathological anatomical findings. They are not the
result of proper embryological studies.
4. Most schematic drawings indicate that, in the con-
ventional theory, the rotation of the foregut is
thought to take place in an “en bloc” fashion.
However, it remains completely obscure which
force should be responsible for this developmental
OBSERVATION ON THE MIDGUT DEVELOPMENT
IN RAT EMBRYOS
In order to demonstrate normal gut development, we
used staged rat embryos, which were studied by means of
a scanning electron microscope (SEM). In this study, the
youngest embryo was aged 13 days and the oldest 18
days. Using microsurgical techniques, the gut loops in-
side the abdomen and in the extraembryonal coelom
In short, the following observations were made:
1. In young embryos (day 13/14) the midgut can be
easily identified as a loop (Fig 1a,b). This loop can
be subdivided in: (a) a central (dorsal) part (b) an
umbilical (ventral) part and (c) a straight part. In
this stage, the colon is already shorter than the
2. In 14-day-old rat embryos, the small gut elongates,
thus pushing the cecum inside the umbilical coelom
Arrows indicate the direction of longitudinal growth of the small
bowel (sb). As a result, the cecum (ce) is pushed to the left, mimick-
Midgut of a 14 days old rat embryo, view from dorsal.
rat embryo. (a) view from the
right, (b) view from ventral. Note
the “physiological herniation”
of the tip of the bowel loop (ce)
into the coelom of the umbilicus.
du ? anlage of the duodenum,
sb ? small bowel, ce ? cecum.
The arrow indicates the pyloric
Midgut of a 13-day-old
276KLUTH, JAESCHKE-MELLI, AND FIEGEL
to the left (so-called “first rotation” of the gut,
3. In a 15-day-old rat embryo the the 3 distinct parts
of the gut loop are clearly discernable (Fig. 3).
a) in the central (dorsal) part, the duodenum is the
main feature. Local growth of the duodenal loop
forces the tip of the duodenojejunal area beneath
the root of the mesentery, which thus reaches its
final anatomical position (Fig 4a, b)
b) In the umbilical part (ventral part) inside the
umbilical coelom, gut loops develop due to
rapid lengthening of the small gut. The position
of the cecum is changing frequently. This seems
to be a phenomenon secondary to the growth of
the intraumbilical loops (Fig 5a, b).
c) In the straight intraabdominal part, growth ac-
tivities are minimal at this time point. Root
(Figs 3 and 5b).
4. At day 17, the so-called “return” of the umbilical
midgut starts in rat embryos (Fig 6). This process is
paralleled by the appearance of loops inside the
abdominal cavity also, which seem to stem from
local growth of jejunal loops (Fig. 4b). The area of
the abdominal cavity into which the loops from the
umbilicus return varies initially. Obviously, the ac-
tual size of the liver and other neighboring organs
influences this developmental step. Interestingly,
not the cecum but the terminal ileum is the final
loop that enters the abdominal cavity (Fig 7).
5. Due to minimal growth activities, the active con-
tribution of the colorectal part to the development
of the midgut loop is only small. The main part of
the colorectum remains inside the abdominal cavity
and only the coecum can be found inside the um-
bilical coelom (Fig 5b). This is in contrast to the
assumption that major parts of the colon can be
found inside the umbilicus.10In the 18-day-old rat
embryo, the cecum enters the abdominal cavity and
takes a ventral position close to the abdominal wall
and the liver. We never saw the cecum (Fig 7) in
the left abdominal cavity or in a more dorsal posi-
tion as it is suggested by some schematic drawings.
6. The straight (intraabdominal) part shows, as the
colorectum, only minimal developmental activities.
This is surprising because rotation, if occurring,
should result in clearly notable morphological
changes in this area (Fig 5b).
The 3 parts of the midgut are easily identifiable. In the central part,
the stomach (st) and the duodenum (du) are seen. Ventrally (umbil-
ical part), small bowel loops (sbl), and the cecum (ce) are found in
side the umbilical cord.
Abdominal cavity and midgut of a 15-day-old rat embryo.
nal region. (a) Rat embryo 15
days old (b) rat embryo 17 days
old. Longitudinal growth of the
duodenum (smaller arrow, du)
forces the tip of the duodenoje-
junal loop beneath the mesen-
teric root (large arrow). sb ?
small bowel, li ? liver Note the
formation of bowel loops (sbl) in
situ in the 17-day-old embryo.
Close up of the duode-
277THE EMBRYOLOGY OF GUT ROTATION
1. Our study indicates that the final position of the gut
inside the abdominal cavity depends on 2 distinct
embryological processes: (a) first, the development
of the duodenal loop and its rapid growth by lon-
gitudinal lengthening in the early phases of devel-
opment. As a result, the tip of the doudenojejunal
loop is pushed beneath the root of the mesentery. It
is obvious that this movement is not the result of
any rotation. (b) The return of the gut into the
abdominal cavity. In all of our embryos, the cecum
entered the right abdominal cavity and was found
ventrally close to the abdominal wall. The reason
for this behavior remains unclear. We can assume,
however, that “free space” in the abdominal cavity
is minimal. Thus, the cecum enters into a position
where space allows.
2. Gut lengthening takes place mainly in the small
gut. This results in the formation of loops inside the
umbilical cord and, later, inside the abdominal cav-
ity. Through these growth activities, the cecum is
pushed into various positions inside the umbilical
cord. This movement must not be mixed up with
rotation. In this stage, a rotation around the axis of
the mesenteric root never takes place.
3. Our observations clearly indicate that mass rotation
bilical (ventral) region of the
midgut loop. (a) View from ven-
tral, embryo approx. 15 days
old. Longitudinal growth of the
small bowel (arrow) leads to
the formation of loops inside
the umbilical cord. The cecum
(ce) moves passively. (b) View
from cranial: note the changed
position of the cecum (ce). The
umbilical cord is filled with
small bowel loops. Note that
signs of rotation around the
axis of the mesenteric vessel
(mv) are missing. Lb ? large
bowel, sb ? small bowel.
Close up of the um-
left, lateral. The colon (ce, co) is entirely inside the abdominal cavity.
The cecum (ce) lies close to the ventral abdominal wall. Re ? rectum.
The arrow points to the last loop inside the umbilical cord (terminal
ileum). bl ? bladder.
Midgut of a rat embryo, approx. 17.5 days old. View from
position of the cecum in the right abdominal cavity. The arrow points
to the terminal ileum which is still inside the umbilical cord. Sbl ?
small bowel loops.
Close up of the ventral part of the midgut loop. Note the
278KLUTH, JAESCHKE-MELLI, AND FIEGEL
of the whole midgut does not take place as indi-
cated by numerous sketches.
In newborns, the normal position of the gut seems to
depend on two distinct embryological processes. Of
these, the proper development of the duodenal loop
seems to be of major importance. This loop appears
through localized growth and lengthening of the duode-
num in an early period of development. Further growth
pushes the tip of the duodenojejunal loop beneath the
mesenteric root, which then reaches its normal position
left to the spine. This process seems to be crucial for the
normal arrangement of the gut inside the abdominal
cavity. This is backed up by clinical observations in
cases of malrotations13: in the vast majority, the duodenal
loop presents with an abnormal course, while the posi-
tion of the cecum is less indicative for the presence of
malrotation. Thus we conclude that in all forms of “iso-
lated” malrotations the improper formation of the duo-
denal loop is the crucial factor.
The other important developmental step is the return
of the intestines from the umbilicus into the abdominal
cavity. During this developmental phase the cecum im-
mediately reaches its final position in the right side of the
abdomen. However, this is not the result of growth
activities but rather that of passiveness.
1. Mall FP: Development of the human intestine and its position in
the adult. Bull Johns Hopkins Hosp 9:197-208, 1898
2. Frazer TE, Robbins RF: On the factors concerned in causing
rotation of the intestine in man. J Anat Physiol 50:74-100, 1915
3. Grob M: U¨ber Lageanomalien des Magen-Darm-Traktes infolge
Sto ¨rungen der fetalen Darmdrehung, Basel, Schwabe, 1953
4. Gross RE: The Surgery of Infancy and Childhood, Philadelphia,
PA, Saunders, 1953
5. Snyder WR Jr, Chaffin L: Embryology and pathology of the intestinal
tract: presentation of forty cases of malrotation. Ann Surg 110:368-380, 1954
6. Pitera JE, Smith VV, Woolf AS, Milla PJ: Embryonic gut anom-
alies in a mouse model of retinoic acid-induced caudal regression
syndrome: delayed gut looping, rudimentary cecum, and anorectal
anomalies. Am J Pathol 159:2321-2329, 2001
7. Baoquan Q, Diez-Pardo JA, Tovar JA: Intestinal rotation in
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8. Gray SW, Skandalakis JE: Embryology for Surgeons, Philadel-
phia, PA, Saunders, 1972, pp 129-141
9. Starck D: Embryologie, Stuttgart, Thieme, 1975, pp 135-
10. Smith EI: Malrotation of the intestine, in Welch KJ, Ran-
dolph JG, Ravitch MM et al. (eds): Pediatric Surgery (ed 4).
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1986, pp 882-895
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12. Schwalbe E: Die Morphologie der Missbildungen des Menschen
und der Tiere. I. Teil Allgemeine Missbildungslehre (Teratologie),
Jena, Gustav Fischer, 1906, pp 143-144
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pokrates, 1976, pp 248-254
279 THE EMBRYOLOGY OF GUT ROTATION