| First Author | Dennison BJC | Year | 2021 |
| Journal | Development | Volume | 148 |
| Issue | 14 | PubMed ID | 34184034 |
| Mgi Jnum | J:308882 | Mgi Id | MGI:6741455 |
| Doi | 10.1242/dev.199448 | Citation | Dennison BJC, et al. (2021) Srsf3 mediates alternative RNA splicing downstream of PDGFRalpha signaling in the facial mesenchyme. Development 148(14):dev199448 |
| abstractText | Signaling through the platelet-derived growth factor receptor alpha (PDGFRalpha) is crucial for mammalian craniofacial development, although the mechanisms by which the activity of downstream intracellular effectors is regulated to mediate gene expression changes have not been defined. We find that the RNA-binding protein Srsf3 is phosphorylated at Akt consensus sites downstream of PI3K-mediated PDGFRalpha signaling in mouse palatal mesenchyme cells, leading to its nuclear translocation. We further demonstrate that ablation of Srsf3 in the mouse neural crest lineage leads to facial clefting due to defective cranial neural crest cell proliferation and survival. Finally, we show that Srsf3 regulates the alternative RNA splicing of transcripts encoding protein kinases in the mouse facial process mesenchyme to regulate PDGFRalpha-dependent intracellular signaling. Collectively, our findings reveal that alternative RNA splicing is an important mechanism of gene expression regulation downstream of PI3K/Akt-mediated PDGFRalpha signaling in the facial mesenchyme and identify Srsf3 as a critical regulator of craniofacial development. |
