Special Reports and ReviewsDevelopment of the human gastrointestinal tract: Twenty years of progress☆,☆☆
Section snippets
Effects of fetal environment on gastrointestinal tract development
Cells of the fetal gastrointestinal tract are exposed to potential extrinsic growth regulators from three sources: (1) the circulation, carrying factors that cross the placenta from the maternal blood, factors produced by the placenta itself, and factors secreted by fetal tissue; (2) the amniotic fluid, carrying factors produced by the extraembryonic membranes or secreted by the fetus; and (3) paracrine and autocrine factors produced by the fetal tissues, which act locally. After birth,
Morphogenesis and differentiation
The esophagus can be identified as a distinct structure early in embryogenesis (4 weeks); it elongates during subsequent development relatively more rapidly than the fetus as a whole.4 At 10 weeks, ciliated columnar epithelium appears in the esophagus. Stratified squamous epithelium replaces it at around 20–25 weeks, a process that begins in the midesophagus and proceeds both caudad and cephalad.68 This process has not been studied further, but development of human fetal esophageal mucosa has
Morphogenesis
The morphological and histological development of the stomach is complete at term.4 Prenatal ultrasound examinations have shown that the fetal stomach grows in a linear fashion from 13 to 39 weeks and that the characteristic anatomic features (greater curvature, lesser curvature, fundus, body, and pylorus) can be identified by 14 weeks. Abnormal images can identify the presence of congenital anomalies. Failure to delineate the fetal stomach ultrasonographically in the second trimester indicates
Morphogenesis
Morphogenesis of the human pancreas has been described in detail previously4 and will be recapitulated only briefly. Formation of the pancreas is initiated by the emergence of dorsal and ventral pancreatic buds on opposite sides of the foregut. As these epithelial buds enlarge, a treelike ductal system develops by growth and branching. As the gut tube grows and rotates, the two pancreatic buds come together and fuse at about the seventh week of gestation. Individual endocrine cells are
Morphogenesis and differentiation
The ontogeny of the small intestine can be thought of as proceeding through three successive phases: morphogenesis and cell proliferation, cell differentiation, and cellular and functional maturation.128 By 13 weeks of gestation, organogenesis of the intestine is complete.129 Organ morphogenesis is well described in standard texts and will not be considered in detail. The major milestones are indicated in Table 1. New data on the process and regulation of cellular differentiation that have
Morphogenesis and differentiation
A striking characteristic of the developing fetal colon is its initial similarity to the small intestine. The development of the colon is marked by three important cytodifferentiative stages: the appearance (from about 8 to 10 weeks) of a primitive stratified epithelium, similar to that found in the early development of the small intestine; the conversion of this epithelium to a villus architecture with developing crypts (about 12–14 weeks); and the remodeling of the epithelium at around 30
Conclusions
Important progress has been made in understanding the development of the human gastrointestinal tract over the last two decades. Techniques of molecular biology have facilitated the analysis of complex mechanisms of developmental regulation, providing model systems capable of elucidating human disorders. Synthesis of data from diverse approaches will be required to define the integrated physiology of the developing gastrointestinal tract and the alterations leading to congenital anomalies.
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Address requests for reprints to: Robert K. Montgomery, Ph.D., Division of Pediatric Gastroenterology and Nutrition, The Floating Hospital for Children, 750 Washington Street, Box 383, Boston, Massachusetts 02111-1533. e-mail: [email protected]; fax: (617) 636-4233.
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Supported in part by National Institutes of Health research grant DK 32658, Pediatric Gastroenterology Research Training grant DK 07471, and Digestive Disease Center grant P30 DK34928.