Figure 4.

Model summarizing the importance of the cholinergic intestinal niche for the maintenance of IES homeostasis based on [65]. (A) Model depicting the proposed role of M3 through EphB/ephrin-B signaling in the ISC niche. (B) Non-neuronal ACh released from tuft cells activates the nicotinic receptor α2β4 localized in Paneth cells and the muscarinic receptor M3 localized in ISCs. α2β4 signaling modulates the expression and release of Wnt5a and Wnt9b. Eventually, proliferation and differentiation of ISCs are enhanced. The M3 signaling directly inhibits and maintains ISC proliferation and differentiation.