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.