PMID- 25865482 OWN - NLM STAT- MEDLINE DCOM- 20150706 LR - 20190108 IS - 1097-4172 (Electronic) IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 161 IP - 3 DP - 2015 Apr 23 TI - Bending gradients: how the intestinal stem cell gets its home. PG - 569-580 LID - S0092-8674(15)00361-X [pii] LID - 10.1016/j.cell.2015.03.041 [doi] AB - We address the mechanism by which adult intestinal stem cells (ISCs) become localized to the base of each villus during embryonic development. We find that, early in gut development, proliferating progenitors expressing ISC markers are evenly distributed throughout the epithelium, in both the chick and mouse. However, as the villi form, the putative stem cells become restricted to the base of the villi. This shift in the localization is driven by mechanically influenced reciprocal signaling between the epithelium and underlying mesenchyme. Buckling forces physically distort the shape of the morphogenic field, causing local maxima of epithelial signals, in particular Shh, at the tip of each villus. This induces a suite of high-threshold response genes in the underlying mesenchyme to form a signaling center called the "villus cluster." Villus cluster signals, notably Bmp4, feed back on the overlying epithelium to ultimately restrict the stem cells to the base of each villus. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Shyer, Amy E AU - Shyer AE AD - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. FAU - Huycke, Tyler R AU - Huycke TR AD - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. FAU - Lee, ChangHee AU - Lee C AD - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. FAU - Mahadevan, L AU - Mahadevan L AD - School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138, USA; Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA; Department of Physics, Harvard University, Cambridge, MA 02138, USA; Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138, USA; Kavli Institute for Nanobio Science and Technology, Harvard University, Cambridge, MA 02138, USA; Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. FAU - Tabin, Clifford J AU - Tabin CJ AD - Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: tabin@genetics.med.harvard.edu. LA - eng GR - F32 DK103563/DK/NIDDK NIH HHS/United States GR - R01 HD047360/HD/NICHD NIH HHS/United States GR - HD047360/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20150409 PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Avian Proteins) RN - 0 (Hedgehog Proteins) RN - 0 (Receptors, G-Protein-Coupled) SB - IM CIN - Cell. 2015 Apr 23;161(3):431-432. doi: 10.1016/j.cell.2015.04.009. PMID: 25910201 MH - Adult Stem Cells/*cytology/metabolism MH - Animals MH - Avian Proteins/analysis/metabolism MH - Biomechanical Phenomena MH - Chick Embryo MH - Hedgehog Proteins/metabolism MH - Intestine, Small/*cytology/embryology/metabolism MH - *Mechanotransduction, Cellular MH - Mice MH - Morphogenesis MH - Receptors, G-Protein-Coupled/analysis MH - Signal Transduction PMC - PMC4409931 MID - NIHMS675970 EDAT- 2015/04/14 06:00 MHDA- 2015/07/07 06:00 PMCR- 2016/04/23 CRDT- 2015/04/14 06:00 PHST- 2014/06/17 00:00 [received] PHST- 2014/10/28 00:00 [revised] PHST- 2015/02/11 00:00 [accepted] PHST- 2015/04/14 06:00 [entrez] PHST- 2015/04/14 06:00 [pubmed] PHST- 2015/07/07 06:00 [medline] PHST- 2016/04/23 00:00 [pmc-release] AID - S0092-8674(15)00361-X [pii] AID - 10.1016/j.cell.2015.03.041 [doi] PST - ppublish SO - Cell. 2015 Apr 23;161(3):569-580. doi: 10.1016/j.cell.2015.03.041. Epub 2015 Apr 9.