title: BMP-mediated induction of GATA4/5/6 blocks somitic responsiveness to SHH.
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 hedgehog-dependent 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.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Georges
authors.initials: G
authors.lastname: Daoud
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Hervé
authors.initials: H
authors.lastname: Kempf
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Kozhemyakina
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Holowacz
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Andreia
authors.initials: A
authors.lastname: Ionescu
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Bldg C-Room 303, 240 Longwood Ave, Boston, MA 02115, USA andrew_lassar@hms.harvard.edu.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lassar
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D019902:Chondrocytes / Q000166:cytology; D050991:GATA4 Transcription Factor / Q000378:metabolism*; D050992:GATA5 Transcription Factor / Q000378:metabolism*; D050993:GATA6 Transcription Factor / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: D019485:Bone Morphogenetic Proteins; D050991:GATA4 Transcription Factor; D050992:GATA5 Transcription Factor; D050993:GATA6 Transcription Factor; C484171:Gata4 protein, mouse; C494756:Gata5 protein, mouse; C494760:Gata6 protein, mouse; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D051741:Kruppel-Like Transcription Factors; C107965:Nkx3-2 protein, mouse; D009687:Nuclear Proteins; C465570:Shh protein, mouse; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse; D000071676:Zinc Finger Protein GLI1
keywords: Chicken; Chondrogenesis; GATA factors; Mouse; NKX3.2; SHH; SOX9