BMP-mediated induction of GATA4/5/6 blocks somatic responsiveness to SHH

Georges Daoud, Hervé Kempf, Deepak Kumar, Elena Kozhemyakina, Tamara Holowacz, Dae Won Kim, Andreia Ionescu, Andrew B. Lassar

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13 Citations (Scopus)

Abstract

The relative timing of SHH and BMP signals controls whether presomitic mesoderm (PSM) cells will adopt either a chondrogenic or lateral plate mesoderm fate. Here we document that SHH-mediated induction of Nkx3.2 maintains the competence of somitic cells to initiate chondrogenesis in response to subsequent BMP signals by repressing BMP-dependent induction of GATA genes. Conversely, administration of BMP signals to PSM or forced expression of GATA family members in chick PSM explants blocks induction of hedgehogdependent gene expression. We demonstrate that GATA factors can interact with Gli factors and can recruit the transcriptional co-factor FOG1 (ZFPM1) to the regulatory region of the mouse Gli1 gene, repressing the induction of Gli1 by SHH by binding to both GATA and Gli binding sites. Knockdown of FOG1 reverses the ability of GATA factors to repress Gli1 expression. Our findings uncover a novel role for GATA transcription factors as repressors of hedgehog signaling, and document that NKX3.2 maintains the ability of sclerotomal cells to express SHH transcriptional targets in the presence of BMP signals by repressing the induction of Gata4/5/6.

Original languageEnglish
Pages (from-to)3978-3987
Number of pages10
JournalDevelopment (Cambridge)
Volume141
Issue number20
DOIs
Publication statusPublished - 2014 Oct 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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    Daoud, G., Kempf, H., Kumar, D., Kozhemyakina, E., Holowacz, T., Kim, D. W., Ionescu, A., & Lassar, A. B. (2014). BMP-mediated induction of GATA4/5/6 blocks somatic responsiveness to SHH. Development (Cambridge), 141(20), 3978-3987. https://doi.org/10.1242/dev.111906