Inequality made equal

Forces generating asymmetry give rise to left–right (LR) differences in internal organs such as the lungs and liver. Now, Yasuhiko Kawakami, Juan Carlos Izpisua Belmonte, and colleagues (Salk Institute, La Jolla, CA), and Julien Vermot and Olivier Pourquié (Stowers Institute for Medical Research, Kansas City, MO) show that these forces are buffered by the action of retinoic acid (RA) to ensure symmetry in vertebrae and muscle formation.

Vertebrae and muscle are derived from the somites, which form as symmetric segmentations along the anterior–posterior axis. These segments form near the node, a mass of cells that provides positional information to organize the body plan. In mice and chicks, the node contains ciliated cells that generate fluid movement to produce LR asymmetry.

The Salk group shows that this ciliated system is conserved in zebrafish. They also find that loss of the system causes asymmetric somite formation. As RA gradients help to time somitogenesis, the authors investigated whether it coordinates the LR system with somite formation. Indeed, blocking RA production led to more somites on the left side, and this asymmetry depended on the LR information flow.

A similar RA buffer also operates in chicks and mice, according to the Missouri group. The details regarding how RA influences LR patterning are not clear. RA down-regulates FGF activity, and this antagonism is known to help time somite formation via oscillations in gene expression. In the absence of RA, these oscillations were faster on the left side than they were on the right.

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