The development of the gastrointestinal tract is a complex and unique process. The gut, unlike other organ systems, is composed of multiple specialized cell types with contributions from three germ layers. The endoderm forms the epithelium of the stomach, intestine, lung, liver, and pancreas. The mesoderm forms both striated (in the esophagus) and smooth muscle that is responsible for peristaltic movements. The neural crest is critical for the enteric nervous system, which controls peristalsis and which is absolutely essential for the proper functioning of the digestive system.
During gastrulation as the endoderm, mesoderm and ectoderm are specified the primitive gut divided into regions with distinct gene expression patterns along the anterior-posterior (AP) axis. These regions are important because each derivative organ is dependent on very diverse developmental programs and to achieve its unique adult function. As cells divide, correct cell positioning within the embryo is required for signaling across germ layers. The interplay between multiple signals and transcription factors is critical in both time and space for correct development. Thus, the primitive gut is divided into foregut, midgut and hindgut. The foregut forms the esophagus, lungs, thyroid, stomach, liver and pancreas. The midgut and hindgut form the small and large intestine (colon), respectively. There are three different mechanisms that are continuously used throughout gut development to maintain regional identity ().
Molecular mechanisms guiding gut development
The first is the use of combinations of transcription factors for tight coordination of gene expression in both time and space (). Master transcriptional regulators are required for both the initial specification of the endoderm as well as the appropriate coordination of downstream factors important for different stages of differentiation. Often, it is combinations of several transcription factors, rather than simple factors, that are required to activate the appropriate downstream gene expression programs. This combinational control helps to fine tune activation of particular sets of genes that execute the final function of the derivate organs.
Second, extracellular signaling factors are required at various times throughout intestinal development (). Interestingly, the same signaling factor may cause different and even opposing downstream effects at different times in ontogeny. For instance, a signal factor that is required early for repression of foregut genes must act later for expression to activate the same genes. A good example of this are the fibroblast growth factors (FGF) and bone morphogenetic proteins (BMP), which represses liver-specific genes in the foregut and later are required in the liver primordium for differentiation.
Third, cell positioning and morphogenesis are critical for appropriate signaling between neighboring tissues during development and homeostasis (). Establishment of the subdivisions of the primitive gut requires the activation of specific transcription factors within the endoderm. Activation of many of these factors requires a signaling input from neighboring tissues, especially the mesoderm. As an example, Wnt signaling in the mesoderm is required for anterior-posterior patterning early in development as well as the maintenance of intestinal progenitor proliferation later in the adult.