期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 47, 页码 15666-15681出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2172-15.2015
关键词
nanos1; neurogenesis; radial precursor development; Smaug2; stem cells; translational repression
资金
- Canadian Institutes of Health Research [MOP-13958]
- Howard Hughes Medical Institute Senior International Research Scholar
- Ontario Graduate Scholarships University of Toronto
- Brain Canada fellowship
Here, we have asked about post-transcriptional mechanisms regulating murine developmental neurogenesis, focusing upon the RNAbinding proteins Smaug2 and Nanos1. We identify, in embryonic neural precursors of the murine cortex, a Smaug2 protein/nanos1 mRNA complex that is present in cytoplasmic granules with the translational repression proteins Dcp1 and 4E-T. We show that Smaug2 inhibits and Nanos1 promotes neurogenesis, with Smaug2 knockdown enhancing neurogenesis and depleting precursors, and Nanos1 knockdown inhibiting neurogenesis and maintaining precursors. Moreover, we show that Smaug2 likely regulates neurogenesis by silencing nanos1 mRNA. Specifically, Smaug2 knockdown inappropriately increases Nanos1 protein, and the Smaug2 knockdownmediated neurogenesis is rescued by preventing this increase. Thus, Smaug2 and Nanos1 function as a bimodal translational repression switch to control neurogenesis, with Smaug2 acting in transcriptionally primed precursors to silence mRNAs important for neurogenesis, including nanos1 mRNA, and Nanos1 acting during the transition to neurons to repress the precursor state.
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