Permissive and instructive Hox codes govern limb positioning

Wang, Y., Hintze, M., Tao, J., Petzsch, P., Köhrer, K., Cheng, L., Liao, Z., Qi, X., Bartolomaeus, T., Schilling, K., Wilting, J., Kuerten, G., Patel, K. and Huang, R. (2026) Permissive and instructive Hox codes govern limb positioning. eLIFE. ISSN 2050-084X doi: 10.7554/eLife.100592.2 (In Press)

Abstract/Summary

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 Hox 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 Hox gene variants in chick embryos to address this issue. Using this approach, we found that Hox4/5 genes are necessary but insufficient for forelimb formation. Within the Hox4/5 expression domain, Hox6/7 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 program depends on the combinatorial actions of these Hox genes. We propose that during the evolutionary emergence of the neck, Hox4/5 provide permissive cues for forelimb formation throughout the neck region, while the final position of the forelimb is determined by the instructive cues of Hox6/7 in the lateral plate mesoderm.

Item Type	Article
URI	https://centaur.reading.ac.uk/id/eprint/128053
Identification Number/DOI	10.7554/eLife.100592.2
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	eLife Sciences Publications
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