
==== Front
Res Sq
ResearchSquare
Research Square
2693-5015
American Journal Experts

39184090
10.21203/rs.3.rs-4882679/v1
10.21203/rs.3.rs-4882679
preprint
1
Article
Villification of the intestinal epithelium is driven by Foxl1
Kaestner Klaus https://orcid.org/0000-0002-1228-021X

Zhu Guoli
Lahori Deeksha
Schug Jonathan
16 8 2024
rs.3.rs-4882679https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
https://www.researchsquare.com/article/rs-4882679/v1
nihpp-rs4882679v1.pdf
Abstract

The primitive gut tube of mammals initially forms as a simple cylinder consisting of the endoderm-derived, pseudostratified epithelium and the mesoderm-derived surrounding mesenchyme. During mid-gestation a dramatic transformation occurs in which the epithelium is both restructured into its final cuboidal form and simultaneously folded and refolded to create intestinal villi and intervillus regions, the incipient crypts. Here we show that the mesenchymal winged helix transcription factor Foxl1, itself induced by epithelial hedgehog signaling, controls villification by activating BMP and PDGFRa as well as planar cell polarity genes in epithelial-adjacent telocyte progenitors, both directly and in a feed- forward loop with Foxo3. In the absence of Foxl1-dependent mesenchymal signaling, villus formation is delayed, the separation of epithelial cells into mitotic intervillus and postmitotic villus cells impaired, and the differentiation of secretory progenitors blocked. Thus, Foxl1 orchestrates key events during the epithelial transition of the fetal mammalian gut.
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