Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling in the facial mesenchyme
| Autor: | Julia Mo, Eric D. Larson, Katherine A. Fantauzzo, Brenna J C Dennison, Rui Fu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Receptor Platelet-Derived Growth Factor alpha Mesenchyme Biology Ligands Mesoderm Mice Phosphatidylinositol 3-Kinases 03 medical and health sciences 0302 clinical medicine Cranial neural crest Growth factor receptor Gene expression medicine Animals Phosphorylation Molecular Biology PI3K/AKT/mTOR pathway 030304 developmental biology Mice Knockout Regulation of gene expression 0303 health sciences Serine-Arginine Splicing Factors Alternative splicing Gene Expression Regulation Developmental RNA-Binding Proteins Neural crest Cell biology Alternative Splicing Phenotype medicine.anatomical_structure Neural Crest Female 030217 neurology & neurosurgery Signal Transduction Research Article Developmental Biology |
| Zdroj: | Development |
| ISSN: | 1477-9129 0950-1991 |
| DOI: | 10.1242/dev.199448 |
| Popis: | Signaling through the platelet-derived growth factor receptor alpha (PDGFRα) 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 PDGFRα 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 PDGFRα-dependent intracellular signaling. Collectively, our findings reveal that alternative RNA splicing is an important mechanism of gene expression regulation downstream of PI3K/Akt-mediated PDGFRα signaling in the facial mesenchyme and identify Srsf3 as a critical regulator of craniofacial development. |
| Databáze: | OpenAIRE |
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