BMP signaling controls buckling forces to modulate looping morphogenesis of the gut
BMP signaling controls buckling forces to modulate looping morphogenesis of the gut
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DOI：
10.1073/pnas.1700307114
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发表时间：
2017-02-28
影响因子：
11.1
通讯作者：
Tabin, Clifford J.
中科院分区：
文献类型：
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作者：
Nerurkar, Nandan L.;Mahadevan, L.;Tabin, Clifford J.
最初直的胚胎肠管的成环是肠形态发生的一个重要方面，允许在体腔的范围内正确放置长小肠。肠袢的形成在给定物种中是高度定型的，并且是由于肠管的差异生长驱动的机械屈曲，因为它对抗薄的弹性膜组织（背肠系膜）的约束而伸长。虽然这一过程的物理学已经被研究过，但其背后的生物学还没有。在这里，我们表明，BMP信号在成环的形态发生的鸟类小肠中起着至关重要的作用。我们首先利用鸡和斑胸草雀肠道形态之间的差异，以确定BMP途径作为一个有前途的候选人，以调节肠道中的差异生长。接下来，关注发育中的小鸡小肠，我们确定背肠系膜中表达的Bmp 2建立了肠管和肠系膜之间的差异伸长率，从而调节将肠管弯曲成环的压缩力。因此，鸡小肠中肠袢的数量和紧密度可以通过调节小肠中BMP活性而直接增加或减少。除了深入了解肠道发育的分子机制外，我们的研究结果还提供了一个生化信号如何作用于组织水平机制以驱动器官发生的例子，并提出了一种可能的机制，通过这种机制可以调节它们以通过进化实现不同的形态。
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.