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XB-ART-2273
Development April 1, 2005; 132 (7): 1511-23.

Inhibition of neurogenesis by SRp38, a neuroD-regulated RNA-binding protein.



Abstract
Although serine-arginine rich (SR) proteins have often been implicated in the positive regulation of splicing, recent studies have shown that one unusual SR protein, SRp38, serves, contrastingly, as a splicing repressor during mitosis and stress response. We have identified a novel developmental role for SRp38 in the regulation of neural differentiation. SRp38 is expressed in the neural plate during embryogenesis and is transcriptionally induced by the neurogenic bHLH protein neuroD. Overexpression of SRp38 inhibits primary neuronal differentiation at a step between neurogenin and neuroD activity. This repression of neuronal differentiation requires activation of the Notch pathway. Conversely, depletion of SRp38 activity results in a dysregulation of neurogenesis. Finally, SRp38 can interact with the peptidyltransferase center of 28S rRNA, suggesting that SRp38 activity may act, in part, via regulation of ribosome biogenesis or function. Strikingly, recent studies of several cell cycle regulators during primary neurogenesis have also revealed a crucial control step between neurogenin and neuroD. SRp38 may mediate one component of this control by maintaining splicing and translational silencing in undifferentiated neural cells.

PubMed ID: 15728676
Article link: Development
Grant support: [+]
Genes referenced: acta4 actc1 actl6a bix1.2 bix1.3 ccnd1 cdknx hba1 id3 myod1 ncam1 neurod1 neurog1 nog notch1 nrp1 sox2 sox3 srsf10 srsf12 tbxt vamp1 vamp2 ventx3.2 wnt8a
Morpholinos: srsf12 MO1 srsf12 MO2


Article Images: [+] show captions


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