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Neural crest-specific deletion of splicing factor Rbfox2 leads to craniofacial abnormalities including cleft palate

ABSTRACT: Alternative splicing (AS) creates proteomic diversity from a limited size genome by generating numerous transcripts from a single protein-coding gene. Tissue-specific regulators of AS are essential components of the gene regulatory network, required for normal cellular function, tissue patterning, and embryonic development. However, their cell-autonomous function in neural crest development has not been explored. Here, we demonstrate that splicing factor Rbfox2 is expressed in the neural crest cells (NCCs) and deletion of Rbfox2 in NCCs leads to cleft palate and defects in craniofacial bone development. RNA-Seq analysis revealed that Rbfox2 regulates splicing and expression of numerous genes essential for neural crest/craniofacial development. We demonstrate that Rbfox2-TGF-β-Tak1 signaling axis is deregulated by Rbfox2 deletion. Furthermore, restoration of TGF-β signaling by Tak1 overexpression can rescue the proliferation defect seen in Rbfox2 mutants. We also identified a positive feedback loop in which TGF-β signaling promotes expression of Rbfox2 in NCCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE127245 | GEO | 2019/07/26

REPOSITORIES: GEO

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Expression profiling in palatal mesenchymal cells stimulated with TGF-beta2 in the presence and absence of TGFbRI and Tak1 kinase inhibitors

Project description:TGF-beta signaling in neural crest cells is required for normal craniofacial development. This signaling can be transduced via TGF-beta type I receptors (TGFbRI) using Smad-dependent or Smad independent signaling pathways. We used microarrays to identify TGF-beta-responsive genes that are dependent either on TGFbRI kinase, Tak1 kinase or both. Primary palatal mesenchymal cell cultures were established. Cultured cells were stimulated with TGF-beta2 in the presence or absence of TGFbRI kinase and Tak1 kinase inhibitors. Unstimulated cells were used as controls. Total RNAs were isolated and hybridized on Affymetrix microarrays.

2013-03-27 | E-GEOD-45491 | biostudies-arrayexpress

Expression profiling in palatal mesenchymal cells stimulated with TGF-beta2 in the presence and absence of TGFbRI and Tak1 kinase inhibitors

2013-03-27 | GSE45491 | GEO

Derivation and characterization of putative craniofacial mesenchymal stromal cells from human induced pluripotent stem cells

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2023-03-11 | PXD038968 | Pride

The BAF chromatin remodeling complex regulates gene expression programs essential for mammalian neural crest development

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P0-cre marked neural crest cells in murine embryo

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2014-06-18 | E-GEOD-52358 | biostudies-arrayexpress

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2014-06-18 | E-GEOD-52357 | biostudies-arrayexpress

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