BMP signaling controls buckling forces to modulate looping morphogenesis of the gut

Nerurkar Nandan L.; Mahadevan L.; Tabin Clifford J.

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BMP signaling controls buckling forces to modulate looping morphogenesis of the gut

机译：BMP signaling controls buckling forces to modulate looping morphogenesis of the gut

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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 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.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第9期|2277-2282|共6页
作者
Nerurkar Nandan L.; Mahadevan L.; Tabin Clifford J.;
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作者单位

Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
intestinal looping; buckling; biomechanics; Bmp; morphogenesis;

BMP signaling controls buckling forces to modulate looping morphogenesis of the gut

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