Peristaltic contractions drive gut anisotropic growth through collective cell rearrangements

The gut is the longest organ in the body, and its length is essential for efficient absorption of nutrient in adults. It is known that the gut undergoes massive elongation during prenatal/embryonic stages1,2, in which anisotropic growth takes place. But how this characteristic organ growth is achieved remains unknown. We here demonstrate an unprecedented role of peristaltic movements in the embryonic gut elongation using a caecum as a novel model in chicken embryos. Inhibition of the peristaltic movements by chemical drugs impedes the elongation of caecum. The elongation-halted caecum restores its longitudinal growth by optogenetically introduced peristaltic movements. At the cellular level, we have found that circular smooth muscle cells divide along the circumferential axis in a peristalsis-independent manner, which would otherwise serve as an engine for the radial growth. However, with peristaltic stimulation, the cells expand collectively their distribution along the gut longitudinal axis leading to the elongation of this organ. Thus, peristaltic activity biases circumferentially proliferating smooth muscle cells toward longitudinal rearrangement. This two-step model offers a novel way to identify the peristaltic activity as a critical growth signal for the gut elongation, and also to parsimoniously explain the anisotropic growth of the gut, which undergoes the elongation while retaining its thickness.