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Permissive and instructive Hox codes govern limb positioning

Year: 2026
Type: preprint
Abstract: 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.
Source: eLife
DOI: 10.7554/elife.100592.2
Authors: Yajun Wang, Maik Hintze, Jinbao Wang, Hengxun Tao, Patrick Petzsch, Karl Köhrer, Longfei Cheng, Peng Zhou, Jianlin Wang, Zhaofu Liao, Xufeng Qi, Dongqing Cai, Thomas Bartolomaeus, Karl Schilling, Joerg Wilting, Stefanie Kuerten, Georgy Koentges, Ketan Patel, Qin Pu, Ruijin Huang
Institutions: Binzhou Medical University, University of Bonn, Ningxia Medical University, Lanzhou University, Heinrich Heine University Düsseldorf, Jinan University, Universitätsmedizin Göttingen, University of Göttingen, University Hospital Bonn, University of Warwick, University of Reading
Language: English
Open Access status: gold
Estimated APC paid: $2,500
OpenAlex ID: W7124842218
Cites: 66
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