Permissive and instructive codes govern limb positioning.

The positioning of limbs along the anterior-posterior axis varies widely across vertebrates. The mechanisms controlling this feature remain to be fully understood. For over 30 years, it has been speculated that genes play a key role in this process, but evidence supporting this hypothesis has been largely indirect. In this study, we employed loss- and gain-of-function gene variants in chick embryos to address this issue. Using this approach, we found that genes are necessary but insufficient for forelimb formation. Within the expression domain, genes are sufficient for reprogramming of neck lateral plate mesoderm to form an ectopic limb bud, thereby inducing forelimb formation anterior to the normal limb field. Our findings demonstrate that the forelimb programme depends on the combinatorial actions of these genes. We propose that during the evolutionary emergence of the neck, provides permissive cues for forelimb formation throughout the neck region, while the final position of the forelimb is determined by the instructive cues of in the lateral plate mesoderm.

© 2024, Wang et al.

PMID: 41949289