Recently, an understanding of the molecular events guiding early development and rotation of the midgut has begun to emerge, with a key role for the dorsal mesentery in generating the left–right asymmetry that allows rotation to take place. The process of midgut formation from trilaminar germ disc to final position of the gut tube is depicted in Fig. .
Fig. 1 Transverse sections showing schema for development of mesodermal germ layer and gut tube. a Day 17, b day 19, c day 20, d day 21. The thin mesodermal sheet gives rise to paraxial mesoderm (future somites), intermediate mesoderm (future excretory units) (more ...)
The key event leading to formation of the dorsal mesentery is the division of the lateral plate mesoderm into its somatic and splanchnic components, creating the coelom or body cavity, at around weeks 3–4 of gestation (Fig. a–g). The forkhead box transcription factor Foxf1
plays a key role in this process. Division of the lateral plate mesoderm is disrupted in mice with targeted knock-out of Foxf1
], with somatic and splanchnic layers either remaining fused together, or with residual points of attachment leading to incomplete separation (Fig. a–d).
Fig. 2 Requirement of normal Foxf1 function for lateral plate differentiation and coelom formation. Differentiation of somatopleure and splanchnopleure and the associated formation of the coelomic cavity is disturbed in Foxf1−/− embryos. a, (more ...)
Following division of the lateral plate mesoderm, Foxf1 expression normally becomes restricted to the splanchnic mesoderm; activation of the homeobox gene Irx3, another marker for lateral plate differentiation, becomes restricted to the somatic mesoderm. In Foxf1 null mice, Irx3 expression is detectable in both somatic and splanchnic mesoderm, suggesting that its expression is normally inhibited by Foxf1.
Recently, initiation of intestinal rotation has been shown to be mediated by key ultrastructural changes in the dorsal mesentery [7
]. Mesenchymal cells on the right side of the mesentery become more sparse and assume a cuboidal appearance, while those on the left side become more densely packed and assume a columnar appearance. As a consequence of this, the dorsal mesentery acquires a tilt to the left (Fig. a, b). This sequence of events is under the molecular control of two transcription factors, Pitx2
. These genes are themselves asymmetrically expressed on the left side of the mesentery, under control of Nodal
, whose expression in the left lateral plate mesoderm is the initial symmetry-breaking event in the embryo.
Fig. 3 Model for the directional looping of the gut tube. See text for additional explanation. a Initially, the gut tube is suspended symmetrically from the dorsal mesentery within the body cavity. b Subsequently, expression of the transcription factors Pitx2 (more ...)
Following tilting of the dorsal mesentery, rapid elongation of the intestine after week 5 combined with rapid growth and expansion of the liver results in temporary herniation of the intestinal loops of the midgut into the umbilical cord [1
]. Coincident with this growth, the small intestine rotates around an axis formed by the superior mesenteric artery, for a total of 270° in an anti-clockwise direction, the process being completed by the time of the return of the intestine to the abdominal cavity during the 10th week (Fig. a–e).
Fig. 4 Normal intestinal rotation. a, b Primary intestinal loop before rotation (lateral view). The superior mesenteric artery forms the axis of the loop and of subsequent rotation. c–e Counter-clockwise rotation of the gut occurs through 270° (more ...)