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dc.contributor.authorNerurkar, Nandan
dc.contributor.authorMahadevan, Lakshminarayanan
dc.contributor.authorTabin, Clifford
dc.date.accessioned2019-07-24T16:04:37Z
dc.date.issued2017-02-13
dc.identifier.citationNerurkar, Nandan L., L. Mahadevan, and Clifford J. Tabin. 2017. BMP Signaling Controls Buckling Forces to Modulate Looping Morphogenesis of the Gut. Proceedings of the National Academy of Sciences of the United States of America 114, no. 9: 2277-2282.en_US
dc.identifier.issn0027-8424en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:40998838*
dc.description.abstractLooping of the initially straight embryonic gut tube is an essential aspect of intestinal morphogenesis, permitting proper placement of the lengthy small intestine within the confines of the body cavity. The formation of intestinal loops is highly stereotyped within a given species and results from differential-growth–driven mechanical buckling of the gut tube as it elongates against the constraint of a thin, elastic membranous tissue, the dorsal mesentery. Although the physics of this process has been studied, the underlying biology has not. Here, we show that BMP signaling plays a critical role in looping morphogenesis of the avian small intestine. We first exploited differences between chicken and zebra finch gut morphology to identify the BMP pathway as a promising candidate to regulate differential growth in the gut. Next, focusing on the developing chick small intestine, we determined that Bmp2 expressed in the dorsal mesentery establishes differential elongation rates between the gut tube and mesentery, thereby regulating the compressive forces that buckle the gut tube into loops. Consequently, the number and tightness of loops in the chick small intestine can be increased or decreased directly by modulation of BMP activity in the small intestine. In addition to providing insight into the molecular mechanisms underlying intestinal development, our findings provide an example of how biochemical signals act on tissue-level mechanics to drive organogenesis, and suggest a possible mechanism by which they can be modulated to achieve distinct morphologies through evolution.en_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dash.licenseLAA
dc.subjectintestinal loopingen_US
dc.subjectbucklingen_US
dc.subjectbiomechanicsen_US
dc.subjectBmpen_US
dc.subjectmorphogenesisen_US
dc.titleBMP Signaling Controls Buckling Forces to Modulate Looping Morphogenesis of the Guten_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America (PNAS)en_US
dash.depositing.authorMahadevan, Lakshminarayanan
dc.date.available2019-07-24T16:04:37Z
dash.workflow.commentsFAR2017en_US
dash.funder.nameNational Institutes of Healthen_US
dash.funder.nameMacArthur Foundationen_US
dash.funder.awardF32 HD069074en_US
dash.funder.awardR01 HD087234en_US
dc.identifier.doi10.1073/pnas.1700307114
dc.source.journalProc Natl Acad Sci USA
dash.source.volume114;9
dash.source.page2277-2282
dash.contributor.affiliatedMahadevan, Lakshminarayanan
dash.contributor.affiliatedTabin, Clifford


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