Neural crest-specific deletion ofin mice 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 ofin 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 bydeletion. Furthermore, restoration of TGF-β signaling by Tak1 overexpression can rescue the proliferation defect seen inmutants. We also identified a positivein which TGF-β signaling promotes expression ofin NCCs.