title: Translational regulation of NeuroD1 expression by FMRP: involvement in glutamatergic neuronal differentiation of cultured rat primary neural progenitor cells.
abstract: 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.
authors: School of Medicine and Neuroscience Research Center, Institute SMART-IABS, Konkuk University, 1 Hwayang-Dong Kwangjin-Gu, Seoul, 143-701, Korea.
authors: Se Jin
authors: SJ
authors: Jeon
authors: Ji-Woon
authors: JW
authors: Kim
authors: Ki Chan
authors: KC
authors: Kim
authors: So Min
authors: SM
authors: Han
authors: Hyo Sang
authors: HS
authors: Go
authors: Jung Eun
authors: JE
authors: Seo
authors: Chang Soon
authors: CS
authors: Choi
authors: Jong Hoon
authors: JH
authors: Ryu
authors: Chan Young
authors: CY
authors: Shin
authors: Mi-Ryoung
authors: MR
authors: Song
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005971:Glutamates / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D005971:Glutamates; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014635:Valproic Acid; C093564:Neurogenic differentiation factor 1