The intestinal epithelium maintains a remarkable balance between proliferation and differentiation despite rapid cellular turnover. A central challenge is to elucidate mechanisms required for robust control of tissue renewal. Opposing WNT and BMP signaling is essential in establishing epithelial homeostasis. However, it has been difficult to disentangle contributions from multiple sources of morphogen signals in the tissue. Here, to dissect epithelial-autonomous morphogenic signaling circuits, we developed an enteroid monolayer culture system that recapitulates four key properties of the intestinal epithelium, namely the ability to maintain proliferative and differentiated zones, self-renew, polarize, and generate major intestinal cell types. We systematically perturb intrinsic and extrinsic sources of WNT and BMP signals to reveal a core morphogenic circuit that controls proliferation, tissue organization, and cell fate. Our work demonstrates the ability of intestinal epithelium, even in the absence of 3D tissue architecture, to control its own growth and organization through morphogen-mediated feedback. Thorne, Chen et al. develop an enteroid monolayer culture system that recapitulates cell-type composition, crypt organization, and turnover kinetics of the intestinal epithelium. The authors use the enteroid monolayer to uncover an epithelium-intrinsic Wnt and BMP morphogenic circuit that regulates proliferation and tissue organization in the intestinal epithelium.
ASJC Scopus subject areas
- Developmental Biology