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Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors

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  • Pallavi Bhattaram

    (and Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute)

  • Alfredo Penzo-Méndez

    (and Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute)

  • Elisabeth Sock

    (Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg)

  • Clemencia Colmenares

    (Cleveland Clinic Lerner Research Institute)

  • Kotaro J. Kaneko

    (National Institute of Child Health and Human Development, National Institutes of Health)

  • Alex Vassilev

    (National Institute of Child Health and Human Development, National Institutes of Health)

  • Melvin L. DePamphilis

    (National Institute of Child Health and Human Development, National Institutes of Health)

  • Michael Wegner

    (Institut für Biochemie, Emil-Fischer-Zentrum, Universität Erlangen-Nürnberg)

  • Véronique Lefebvre

    (and Orthopaedic and Rheumatologic Research Center, Cleveland Clinic Lerner Research Institute)

Abstract

During organogenesis, neural and mesenchymal progenitor cells give rise to many cell lineages, but their molecular requirements for self-renewal and lineage decisions are incompletely understood. In this study, we show that their survival critically relies on the redundantly acting SoxC transcription factors Sox4, Sox11 and Sox12. The more SoxC alleles that are deleted in mouse embryos, the more severe and widespread organ hypoplasia is. SoxC triple-null embryos die at midgestation unturned and tiny, with normal patterning and lineage specification, but with massively dying neural and mesenchymal progenitor cells. Specific inactivation of SoxC genes in neural and mesenchymal cells leads to selective apoptosis of these cells, suggesting SoxC cell-autonomous roles. Tead2 functionally interacts with SoxC genes in embryonic development, and is a direct target of SoxC proteins. SoxC genes therefore ensure neural and mesenchymal progenitor cell survival, and function in part by activating this transcriptional mediator of the Hippo signalling pathway.

Suggested Citation

  • Pallavi Bhattaram & Alfredo Penzo-Méndez & Elisabeth Sock & Clemencia Colmenares & Kotaro J. Kaneko & Alex Vassilev & Melvin L. DePamphilis & Michael Wegner & Véronique Lefebvre, 2010. "Organogenesis relies on SoxC transcription factors for the survival of neural and mesenchymal progenitors," Nature Communications, Nature, vol. 1(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:1:y:2010:i:1:d:10.1038_ncomms1008
    DOI: 10.1038/ncomms1008
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    Cited by:

    1. Bieke Decaesteker & Amber Louwagie & Siebe Loontiens & Fanny De Vloed & Sarah-Lee Bekaert & Juliette Roels & Suzanne Vanhauwaert & Sara De Brouwer & Ellen Sanders & Alla Berezovskaya & Geertrui Deneck, 2023. "SOX11 regulates SWI/SNF complex components as member of the adrenergic neuroblastoma core regulatory circuitry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jasmien Roosenboom & Myoung Keun Lee & Jacqueline T Hecht & Carrie L Heike & George L Wehby & Kaare Christensen & Eleanor Feingold & Mary L Marazita & A Murat Maga & John R Shaffer & Seth M Weinberg, 2018. "Mapping genetic variants for cranial vault shape in humans," PLOS ONE, Public Library of Science, vol. 13(4), pages 1-14, April.
    3. Keira J A Johnston & Joey Ward & Pradipta R Ray & Mark J Adams & Andrew M McIntosh & Blair H Smith & Rona J Strawbridge & Theodore J Price & Daniel J Smith & Barbara I Nicholl & Mark E S Bailey, 2021. "Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank," PLOS Genetics, Public Library of Science, vol. 17(4), pages 1-27, April.
    4. Marco Angelozzi & Anirudha Karvande & Véronique Lefebvre, 2024. "SOXC are critical regulators of adult bone mass," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

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