{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang 110866, China",
    "School of Basic Medical Science, Chengde Medical University, Chengde 067000, Hebei, China",
    "Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yining Tang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shibin Bai",
      "orcid": "0000-0002-0218-8524"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shanshan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Mao",
      "orcid": "0009-0004-8792-1888"
    },
    {
      "affs": [
        0
      ],
      "name": "Wanyi Dang",
      "orcid": "0000-0001-6097-8367"
    },
    {
      "affs": [
        0
      ],
      "name": "Huiling Xue",
      "orcid": "0000-0001-8616-5815"
    },
    {
      "affs": [
        0
      ],
      "name": "Songyang Shang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ziqiu Jia",
      "orcid": "0000-0002-9719-5240"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoping Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanlei Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaona Xu"
    },
    {
      "affs": [
        2
      ],
      "name": "David M. Irwin",
      "orcid": "0000-0001-6131-4933"
    },
    {
      "affs": [
        0
      ],
      "name": "Junpeng Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuyi Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhe Wang",
      "orcid": "0000-0002-8166-1059"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b6268tcxy10d1.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2605261123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13715784/",
  "id": "b6268tcxy10d1",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2605261123",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "412"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Developmental Biology"
    ],
    [
      "openalex",
      "1312|Developmental Biology and Gene Regulation"
    ]
  ],
  "openalex": "W7223063582",
  "pdf_url": null,
  "pmcid": "PMC13715784",
  "pmid": "42900719",
  "published": "2026-10-20",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/b6268tcxy10d1.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T12:22:59Z",
      "native_id": "PMC13715784",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2605261123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Developmental Biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "Lhx9 specifically modulates phalanx number, whereas Lhx2 constrains digit length in tetrapods",
  "title_text": "Lhx9 specifically modulates phalanx number, whereas Lhx2 constrains digit length in tetrapods",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:22:59Z",
  "url": "https://research.draconitic.com/paper/b6268tcxy10d1",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}