Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish.

How adjacent organ fields communicate during development is not understood. Here, we identify a mechanism in which signaling within the forelimb field restricts the potential of the neighboring heart field. In zebrafish embryos deficient in retinoic acid (RA) signaling, the pectoral fins (forelimbs) are lost while both chambers of the heart are enlarged. We provide evidence that both of these phenotypes are due to RA signaling acting directly within the forelimb field. hoxb5b, an RA-responsive gene expressed within the forelimb field, is required to restrict the number of atrial cells arising from the adjacent heart field, although its function is dispensable for forelimb formation. Together, these data indicate nonautonomous influences downstream of RA signaling that act to limit individual chamber size. Therefore, our results offer new perspectives on the mechanisms regulating organ size and the possible causes of congenital syndromes affecting both the heart and forelimb.