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Planar Enteroids Reveal an Autonomous WNT And BMP Circuit Controlling Intestinal Epithelial Growth and Organization
Author(s) -
Thorne Curtis A.,
Chen Ina W.,
Sanman Laura E.,
Cobb Melanie H.,
Wu Lani F.,
Altschuler Steven J.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.659.14
Subject(s) - wnt signaling pathway , microbiology and biotechnology , morphogen , biology , intestinal epithelium , epithelium , stem cell , cell fate determination , developmental biology , morphogenesis , signal transduction , genetics , transcription factor , gene
The epithelial lining of the human intestine is a prime example of tight homeostatic control of cell proliferation, organization and fate determination. As a mechanism for dealing with constant mechanical, chemical and pathogen‐derived insults, the epithelium is in constant turnover, completely renewing every four days. Amazingly, this active process produces multiple cell types at just the right ratios and locations throughout our life span. Failure of this exquisite control is the basis for diseases including Crohn's disease, ulcerative colitis, and cancers of the esophagus, stomach, small and large intestine. 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 morphogenic signals in the tissue. Here, to dissect epithelial‐autonomous morphogenic signaling circuits, we developed a planar enteroid intestinal culture system that recapitulates key properties of the intestinal epithelium, specifically 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. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .