{
  "abstract": "How changes in conserved developmental genetic programs contribute to morphological evolution remains poorly understood, particularly in non-conventional model species. Here, we combine single-cell transcriptomic and chromatin-accessibility profiling with cross-species label transfer and gene regulatory network inference to compare mouse and pig limb development. Our analyses identify broadly conserved cellular organization but discrete divergence in HOX-, FGF- and SHH-regulated programs. FGFR inhibition in mouse limb buds phenocopies the distal expansion of pig GREM1 expression, while altered SHH responses and anterior-posterior polarity converge on the PTCH1 regulatory landscape. Its functional dissection reveals degeneration of a limb regulatory module in artiodactyls, conservation of an additional distal enhancer, and extensive redundancy among cis-regulatory inputs. Allele-specific analyses further show that reduced Ptch1 dosage is buffered by transcriptional compensation. Together, these findings reveal how cis-regulatory and pathway-level robustness can accommodate distributed regulatory change while preserving developmental function, providing a mechanistic framework for the evolution of artiodactyl limb morphology.",
  "abstract_shown": true,
  "affiliations": [
    "Centro Andaluz de Biologia del Desarrollo (CABD-CSIC), Sevilla, Spain"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "A. Alcaina-Caro"
    },
    {
      "name": "I. Sospedra-Arrufat"
    },
    {
      "name": "V. Tissieres"
    },
    {
      "name": "I. Salvador-Martinez"
    },
    {
      "name": "L. Almorox"
    },
    {
      "name": "J. J. Pawluk"
    },
    {
      "name": "A. Diaz-Rueda"
    },
    {
      "name": "A. Fernandez-Minan"
    },
    {
      "name": "A. Hurtado"
    },
    {
      "name": "F. Martinez Real"
    },
    {
      "name": "D. Lupianez"
    },
    {
      "name": "B. Pernaute"
    },
    {
      "name": "A. Visel"
    },
    {
      "name": "M. Osterwalder"
    },
    {
      "name": "H. Heyn"
    },
    {
      "name": "J. J. Tena"
    },
    {
      "name": "G. Nusspaumer"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Lopez-Rios"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6mj3hdq4vz7xe.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.07.765081",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.07.765081v1.full",
  "id": "6mj3hdq4vz7xe",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.07.765081v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "developmental biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.07.765081v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6mj3hdq4vz7xe.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:30:16Z",
      "native_id": "10.64898/2026.11.07.765081",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.07.765081v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:developmental biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "Network inference at single-cell resolution reveals morphoregulatory divergence and multilayered buffering in limb evolution",
  "title_text": "Network inference at single-cell resolution reveals morphoregulatory divergence and multilayered buffering in limb evolution",
  "type": "preprint",
  "updated_at": "2026-11-10T00:30:16Z",
  "url": "https://research.draconitic.com/paper/6mj3hdq4vz7xe",
  "venue": "bioRxiv",
  "versions": []
}