Authors
Yining Tang, Shibin Bai, Shanshan Li, Ying Mao, Wanyi Dang, Huiling Xue, Songyang Shang, Ziqiu Jia, Xiaoping Li, Yanlei Liu, Xiaona Xu, David M Irwin, Junpeng Zhang, Shuyi Zhang, Zhe Wang
Published in
Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 43. Pages e2605261123. Oct 27, 2026. Epub Oct 20, 2026.
Abstract
Most nonmammalian tetrapods exhibit more than three phalanges in their posterior digits (III-V), whereas mammals are restricted to no more than three. So far, the molecular mechanism underlying this evolutionary reduction and the functions of Lhx2 and Lhx9 in digit development remain unclear. Here we show divergent evolution of Lhx2 and Lhx9 expression patterns in embryonic limbs across tetrapods. We further demonstrate that although ectopic overexpression of each gene in chick embryos delayed limb skeletal development, only Lhx9 reduced the phalanx number in the posterior digits. Transcriptomic analysis showed that Lhx2 regulates pathways for chondrocyte and osteoblast differentiation, and Lhx9 preferentially influences skeletal segmentation via the bone morphogenetic protein (BMP) pathway. The unique function and differential expression of Lhx9 in the limb buds between mammals and nonmammalian tetrapods suggest it may have acquired a role in suppressing phalanx number, driving the evolutionary reduction of phalanx number in mammals.
PMID:
42900719
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.
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