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.
Highlights
IntroductionCraniofacial and cardiovascular abnormalities are the most common defects, contributing to more than one-third of the congenital diseases
3–4% of infants are born with congenital diseases
To compare Rbfox2 expression with a known neural crest cell marker, we performed Rbfox2 and Pax3 immunostaining on transverse sections from E9.5, E10.5 and E11.5 embryos (Figure 1P–U)
Summary
Craniofacial and cardiovascular abnormalities are the most common defects, contributing to more than one-third of the congenital diseases. Proper formation of these structures involves intricate processes such as proliferation, migration, and differentiation of NCCs, as well as their interaction with neighboring cells (Martik and Bronner, 2017; Plein et al, 2015). Lineage-tracing experiments in mouse embryos have demonstrated that NCCs differentiate into a diverse array of cell types including the craniofacial skeletal elements, autonomous nervous system of the heart and GI-tract, as well as smooth muscle cells of the cardiac OFT (Chai et al, 2000; Jiang et al, 2002; Jiang et al, 2000; Lee et al, 2004; Martik and Bronner, 2017; Plein et al, 2015; Waldo et al, 1999; Yoshida et al, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
