![]() ![]() The mechanism of selection between enteroendocrine, goblet, and Paneth cells remains unclear, and additional factors are hypothesized to direct differentiation of goblet and Paneth cells. Additional transcription factors such as Ngn3, Pdx1, and Neurod1 are required for terminal differentiation of enteroendocrine cells ( Schonhoff et al. Progenitors that express Hes1 will differentiate into absorptive enterocytes, whereas progenitors that express Math1 are committed to the secretory lineage and thus fated to become goblet, Paneth, or enteroendocrine cells. The current model of intestinal epithelial differentiation suggests that β-catenin drives production of a pool of multipotent progenitors that use Notch signaling to select between Math1 or Hes1 expression ( Yang et al. ![]() β-Catenin signaling is also necessary for stem cell renewal, proliferation, and differentiation ( Pinto et al. Several genes have been implicated in crypt morphogenesis and proliferation, including Wnt/β-catenin pathway members and target genes such as Cdx1 and Cdx2 ( Korinek et al. The molecular mechanisms that underlie crypt formation and intestinal cell fate specification remain incompletely defined. ![]() Absorptive enterocytes, goblet, and enteroendocrine cells migrate up the villus, whereas Paneth cells migrate down to reside at the crypt base. Near the top of the crypt, these daughter cells terminally differentiate into the four main cell types of the intestinal epithelium. All of these cell types derive from multipotent stem cells residing near the base of the Crypts of Liberkühn, the proliferative compartment of the intestinal epithelium ( Madara and Trier 1994).ĭifferentiation within the crypts follows a spatial distribution: The stem cells are located near the base of the crypts and give rise to daughter cells that migrate up as they proliferate. The epithelium of the small intestine is a highly proliferative tissue composed of four distinct cell types: absorptive enterocytes and three secretory lineages consisting of mucus-secreting goblet cells, hormone-secreting enteroendocrine cells, and antimicrobial peptide-secreting Paneth cells. ![]()
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