{
  "abstract": "Pathogenic variants in the genes encoding the non-canonical TGFB signaling components TAK1 (MAP3K7 ) , TAB2 and PKA-Cα (PRKACA) cause rare multisystem disorders, which may include congenital heart disease (CHD). To investigate the role of TAK1 signaling in CHD, we performed genetic analysis of CHD patients and discovered an increased burden of rare TAB2 and TAK1 variants in patients with extracardiac abnormalities. To address the mechanism of TAK1 in heart development, we performed experiments in cell and animal models. Zebrafish tak1 and tab2 mutants presented with cardiac and extracardiac developmental defects, and tak1 mutant hearts showed downregulation of genes encoding core cardiac transcription factors, sarcomeric proteins and extracellular matrix proteins. In vitro experiments indicated that TAK1 via TAB2 and PKA-Cα is activated at the primary cilium during cardiomyogenesis; activation at this site is enhanced by TGFB/BMP ligands. Inactivation of TAK1 inhibited ciliary signaling and cardiomyocyte differentiation, and patient-derived TAK1 variants reduced its ciliary localization. In conclusion, our data establish a pivotal role for TAK1 and its upstream regulators at the primary cilium in heart development and syndromic CHD.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark",
    "Department of Biology, University of Copenhagen, Copenhagen, Denmark",
    "Department of Medical Genetics, Carl von Ossietzky University, Oldenburg, Germany",
    "Faculty of Health and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain",
    "ZeClinics SL, Badalona, Spain",
    "Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, New Zealand",
    "Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand",
    "Aix Marseille Université, INSERM, MMG U1251, Marseille, France",
    "College of Health Sciences, VinUniversity, Hanoi, Vietnam"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Canan Doğanlı",
      "orcid": "0000-0002-5230-0801"
    },
    {
      "affs": [
        1,
        0
      ],
      "name": "Oskar Kaaber Thomsen",
      "orcid": "0009-0003-5513-7397"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Daniel A. Baird",
      "orcid": "0009-0004-5711-302X"
    },
    {
      "affs": [
        1
      ],
      "name": "Yeasmeen Ali",
      "orcid": "0000-0001-5895-1210"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Menachem Viktor Sarusie",
      "orcid": "0000-0003-4341-9787"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Enrique Audain",
      "orcid": "0000-0002-9201-7840"
    },
    {
      "affs": [
        1,
        0
      ],
      "name": "Line Jeanett Jessen"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Pauline Munck Truelsen"
    },
    {
      "affs": [
        1
      ],
      "name": "Johanne Bay Mogensen",
      "orcid": "0000-0001-6317-9114"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "Maria Schrøder Holm"
    },
    {
      "affs": [
        3,
        4,
        0
      ],
      "name": "Kateřina Apolínová",
      "orcid": "0009-0002-2066-7374"
    },
    {
      "affs": [
        0
      ],
      "name": "Lorenzo Buttò",
      "orcid": "0009-0004-9270-2284"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Maria Diamanti"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Jindřiška Leischner Fialová",
      "orcid": "0000-0002-7314-1432"
    },
    {
      "affs": [
        6,
        5
      ],
      "name": "Emma M. Wade",
      "orcid": "0000-0003-2990-0232"
    },
    {
      "affs": [
        6,
        1
      ],
      "name": "Stephen P. Robertson",
      "orcid": "0000-0002-5181-7809"
    },
    {
      "affs": [
        1,
        7
      ],
      "name": "Lotte Bang Pedersen",
      "orcid": "0000-0002-9749-3758"
    },
    {
      "affs": [
        7
      ],
      "name": "Laurent Argiro",
      "orcid": "0000-0003-3946-2934"
    },
    {
      "affs": [
        7,
        2
      ],
      "name": "Fabienne Lescroart",
      "orcid": "0000-0003-4942-7921"
    },
    {
      "affs": [
        2,
        1
      ],
      "name": "Marc‐Phillip Hitz",
      "orcid": "0000-0001-9894-6897"
    },
    {
      "affs": [
        1,
        0
      ],
      "name": "Søren T. Christensen",
      "orcid": "0000-0001-5004-304X"
    },
    {
      "affs": [
        8,
        0
      ],
      "name": "Lars Allan Larsen",
      "orcid": "0000-0002-7536-1172"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/daqk5e38xq7ey.bib",
  "cited_by": 15,
  "doi": "10.1371/journal.pbio.3003902",
  "fulltext_url": null,
  "id": "daqk5e38xq7ey",
  "issns": [
    "1544-9173",
    "1545-7885"
  ],
  "landing_url": "https://doi.org/10.1371/journal.pbio.3003902",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Congenital heart defects research"
    ]
  ],
  "openalex": "W4396749355",
  "pdf_url": "https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3003902&type=printable",
  "pmcid": "PMC13436766",
  "pmid": "42550797",
  "published": "2026-08-04",
  "publisher": "Public Library of Science",
  "ris": "https://research.draconitic.com/paper/daqk5e38xq7ey.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W4396749355",
      "source": "openalex",
      "url": "https://doi.org/10.1371/journal.pbio.3003902"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Congenital heart defects research",
      "subfield": "molecular-biology"
    }
  ],
  "title": "TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development",
  "title_text": "TAK1 operates at the primary cilium in non-canonical TGFB/BMP signaling to control heart development",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/daqk5e38xq7ey",
  "venue": "PLoS Biology",
  "versions": []
}