title: BMP signaling controls buckling forces to modulate looping morphogenesis of the gut.
abstract: Looping 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 thatBmp2expressed 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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115.
authors.forename: Nandan L
authors.initials: NL
authors.lastname: Nerurkar
authors.affiliation: School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138; tabin@genetics.med.harvard.edu lm@seas.harvard.edu.|Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138.|Department of Physics, Harvard University, Cambridge, MA 02138.|Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, MA 02138.|Kavli Institute for Bionano Science and Technology, Harvard University, Cambridge, MA 02138.
authors.forename: L
authors.initials: L
authors.lastname: Mahadevan
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, MA 02115; tabin@genetics.med.harvard.edu lm@seas.harvard.edu.
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Tabin
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000235:genetics* / Q000378:metabolism; D001696:Biomechanical Phenomena; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002642:Chick Embryo; D002645:Chickens; D046369:Finches; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism*; D040542:Mechanotransduction, Cellular; D008643:Mesentery / Q000033:anatomy & histology / Q000254:growth & development / Q000378:metabolism; D009024:Morphogenesis / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D030161:Avian Proteins; D055396:Bone Morphogenetic Protein 2; D002352:Carrier Proteins; D049452:Green Fluorescent Proteins; D000099176:Noggin Protein
keywords: Bmp; biomechanics; buckling; intestinal looping; morphogenesis