Translational regulation of NeuroD1 expression by FMRP: involvement in glutamatergic neuronal differentiation of cultured rat primary neural progenitor cells.

Authors: Jeon, Se Jin  Kim, Ji-Woon  Kim, Ki Chan  Han, So Min  Go, Hyo Sang  Seo, Jung Eun  Choi, Chang Soon  Ryu, Jong Hoon  Shin, Chan Young  Song, Mi-Ryoung 
Citation: Jeon SJ, etal., Cell Mol Neurobiol. 2014 Mar;34(2):297-305. doi: 10.1007/s10571-013-0014-9. Epub 2013 Dec 12.
Pubmed: (View Article at PubMed) PMID:24338128
DOI: Full-text: DOI:10.1007/s10571-013-0014-9

Fragile X mental retardation protein (FMRP) is encoded by Fmr1 gene in which mutation is known to cause fragile X syndrome characterized by mental impairment and other psychiatric symptoms similar to autism spectrum disorders. FMRP plays important roles in cellular mRNA biology such as transport, stability, and translation as an RNA-binding protein. In the present study, we identified potential role of FMRP in the neural differentiation, using cortical neural progenitor cells from Sprague-Dawley rat. We newly found NeuroD1, an essential regulator of glutamatergic neuronal differentiation, as a new mRNA target interacting with FMRP in co-immunoprecipitation experiments. We also identified FMRP as a regulator of neuronal differentiation by modulating NeuroD1 expression. Down-regulation of FMRP by siRNA also increased NeuroD1 expression along with increased pre- and post-synaptic development of glutamatergic neuron, as evidenced by Western blot and immunocytochemistry. On the contrary, cells harboring FMRP over-expression construct showed decreased NeuroD1 expression. Treatment of cultured neural precursor cells with a histone deacetylase inhibitor, valproic acid known as an inducer of hyper-glutamatergic neuronal differentiation, down-regulated the expression of FMRP, and induced NeuroD1 expression. Our study suggests that modulation of FMRP expression regulates neuronal differentiation by interaction with its binding target mRNA, and provides an example of the gene and environmental interaction regulating glutamatergic neuronal differentiation.


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RGD ID: 11667958
Created: 2017-01-19
Species: All species
Last Modified: 2017-01-19
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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.