发育生物学与再生医学：Development of the Digestive System.ppt

Wnt signaling promotes cell proliferation and confers competence for the full range of modes of differentiation, while preventing differentiation from occurring immediately——maintains the stem cells. Wnt signaling activates the expression of Notch pathway components. Notch signaling mediates lateral inhibition——forces the cells to diversify. Cells expressed Notch ligands escape from Notch activation themselves—differentiate as secretory cells. Cells express Notch and retain competence to differentiate and to engage in lateral-inhibition competition with their neighbors. Both classes of cells continue dividing so long as they are in the crypt, under the influence of Wnt. But when cells leave the crypt and lose exposure to Wnt signaling, division stops, and the cells differentiate according to their individual states of Notch activation at that time—as absorptive cells if Notch is activated, as secretory cells if it is not. 4. Wnt, Hedgehog, and BMP Signaling Pathways Combine to Delimit the Stem-Cell Niche The gut stem cells cannot exist without the special environment that the crypt provides for them. This stem cell niche is as essential as the stem cells themselves. ? How is it created and maintained? Summary In the small intestine, stem cells in the crypts generate new absorptive, goblet, enteroendocrine, and Paneth cells, replacing most of the epithelial lining of the intestine every week. Wnt signaling in the crypts maintains the stem-cell population, Notch signaling drives diversification of the stem-cell progeny and limits the number that are consigned to a secretory fate. Cell–cell interactions within the epithelium mediated by ephrin–Eph signaling control the selective migration of cells from the crypts upward onto the villi. Interactions between the epithelium and the stroma, involving the Wnt, Hedgehog, and BMP pathways organize the pattern of crypts and villi, thereby creating the niches that stem cells inhabit. Hhex and Gata are required