The genetic control of gut regionalization relies on a hierarchy of molecular events in which the Hox gene family
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چکیده
The study of gut patterning provides a paradigm for the dissection of mechanisms involved in organogenesis. In mice and chick, the gut is derived from two endodermal folds, first the anterior intestinal portal and then later the caudal intestinal portal, that fuse ventrally and move towards each other, joining at the yolk stalk level (Grapin-Botton and Melton, 2000; Roberts, 2000). Concomitantly, the endoderm recruits the splanchnic mesenchyme, and crosstalk between these cell layers leads to the acquisition of regional characteristics along the rostrocaudal gut axis. The esophagus and the stomach originate from the foregut, that also gives rise to the thyroid, lung, liver and pancreas. The midgut develops into the digestive region of the gastrointestinal (GI) tract, while the hindgut forms the colon. Both extremities of the gut, the mouth and the rectum, are mostly ectoderm derivatives. Whereas gross anatomical boundaries delineate the GI tract, subtle morphological and functional differences progressively arise at late embryonic and postnatal stages (Gordon and Hermiston, 1994). Stomach development illustrates this acquisition of highly specialized features. The stomach emerges as a bulge at around embryonic day (E) 10.0. Its poorly differentiated epithelium undergoes extensive remodeling to generate a complex and continuously renewing epithelium during adulthood. The stomach epithelium of adult mice is squamous in its proximal part (forestomach) and glandular distally (hindstomach). The latter contains multiple invaginations into the lamina propria, known as gastric units. The mechanisms that regulate progressive regional and functional cell specification of the gut, and particularly that of the stomach, remain largely unknown, but experimental evidence has established that gut patterning depends on mesenchymal-epithelial interactions. Identified participating signaling molecules include hedgehog (Hh), transforming growth factor β (Tgfβ) and fibroblast growth factor (Fgf) family members, as well as their associated receptors. Sonic hedgehog (Shh) and Indian hedgehog (Ihh) genes coordinate patterning and organogenesis of the gut and its derivatives (Roberts et al., 1995; Chiang et al., 1996; Apelqvist et al., 1997; Litingtung et al., 1998; Pipecelli et al., 1998; Roberts et al., 1998; Takahashi et al., 1998; Hebrok et al., 2000; RamalhoSantos et al., 2000; Sukegawa et al., 2000). They are expressed in a complementary fashion in the embryonic stomach, Shh and Ihh transcripts being detected in the foreand hindstomach, respectively (Bitgood and McMahon, 1995). In Shh mutants, the gastric epithelium displays overgrowth and intestinal characteristics. Smooth muscle patterning in the gut also depends on Shh and Ihh (Ramalho-Santos et al., 2000; Sukegawa et al., 2000). 4075 Development 129, 4075-4087 (2002) Printed in Great Britain © The Company of Biologists Limited 2002 DEV4591
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