Intestinal cell stemness, proliferation and differentiation are complex processes all occurring in distinct compartments of the crypt that need to be closely regulated to ensure proper epithelial renewal. The involvement of the Hippo pathway in intestinal epithelial proliferation and regeneration after injury via the regulation of its effectors YAP1 and TAZ has been well-documented over the last decade. The implication of YAP1 and TAZ on intestinal epithelial cell differentiation is less clear. Using intestinal cell models in which the expression of YAP1 and TAZ can be modulated, our group showed that YAP1 inhibits differentiation of the two main intestinal epithelial cell types, goblet and absorptive cells through a specific mechanism involving the repression of prodifferentiation transcription factor CDX2 expression. Further analysis provided evidence that the repressive effect of YAP1 on intestinal differentiation is mediated by regulation of the Hippo pathway by Src family kinase activity. Interestingly, the TAZ paralog does not seem to be involved in this process, which provides another example of the lack of perfect complementarity of the two main Hippo effectors.
Keywords: Hippo pathway; TAZ; YAP1; differentiation; epithelium; intestine.
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