title: The autism-related gene SNRPN regulates cortical and spine development via controlling nuclear receptor Nr4a1.
abstract: The small nuclear ribonucleoprotein polypeptide N (SNRPN) gene, encoding the RNA-associated SmN protein, duplications or deletions of which are strongly associated with neurodevelopmental disabilities. SNRPN-coding protein is highly expressed in the brain. However, the role of SNRPN protein in neural development remains largely unknown. Here we showed that the expression of SNRPN increased markedly during postnatal brain development. Overexpression or knockdown of SNRPN in cortical neurons impaired neurite outgrowth, neuron migration, and the distribution of dendritic spines. We found that SNRPN regulated the expression level of Nr4a1, a critical nuclear receptor during neural development, in cultured primary cortical neurons. The abnormal spine development caused by SNRPN overexpression could be fully rescued by Nr4a1 co-expression. Importantly, we found that either knockdown of Nr4a1 or 3, 3'- Diindolylmethane (DIM), an Nr4a1 antagonist, were able to rescue the effects of SNRPN knockdown on neurite outgrowth of embryonic cortical neurons, providing the potential therapeutic methods for SNRPN deletion disorders. We thus concluded that maintaining the proper level of SNRPN is critical in cortical neurodevelopment. Finally, Nr4a1 may serve as a potential drug target for SNRPN-related neurodevelopmental disabilities, including Prader-Willi syndrome (PWS) and autism spectrum disorders (ASDs).
authors.affiliation: Department of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shifang
authors.initials: S
authors.lastname: Shan
authors.affiliation: Department of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Department of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai 201102, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Xu
mesh_terms: D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting / Q000235:genetics; D006801:Humans; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D055517:snRNP Core Proteins / Q000235:genetics*
chemical_list: D001324:Autoantigens; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D055517:snRNP Core Proteins