Scientists unlock the secrets of gut coil development

By The Science Advisory Board staff writers

September 26, 2022 -- Scientists now have a better understanding of embryo gut development: They've learned the counterclockwise gut rotation that occurs when the organ is formed is orchestrated by two waves of the transcription factor Pitx2. The findings have implications for diagnosing and preventing birth defects, such as intestinal malrotation and volvulus.

The Nodal gene induces the first wave of Pitx2 to develop organs, but Nodal's presence is short-lived. Once it stimulates Pitx2 expression, it disappears before gut rotation occurs. Until now, scientists weren't clear on how Pitx2 stays active to direct gut rotation when Nodal is gone.

The research team from Cornell University found that a sensor, TGF-beta, lies latent until it gets activated by the dorsal mesentery that attaches to and holds the gut tube in place (Science, September 23, 2022). To direct rotation, the dorsal mesentery tissue expands on the right side and compacts on the left, which TGF-beta senses and then activates the second Pitx2 wave.

The scientists used engineered mice and chicken embryos whereby they opened "windows" in the eggshell so development could be observed and gene expression manipulated. A probe in live embryos measured stiffness and elasticity in the dorsal mesentery. The measurements demonstrated expansion on the right side and TGF-beta-Pitx2 induced braking on the left side, which created a tilt in the tissue to allow for gut tube looping.

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