title: Developmental profiling of ASD-related shank3 transcripts and their differential regulation by valproic acid in zebrafish.
abstract: SHANK3 is a scaffolding protein that binds to various synaptic proteins at the postsynaptic density (PSD) of excitatory glutamatergic synapses. SHANK3 is not only strongly implicated in autism spectrum disorders (ASD) but also plays a critical role in human Phelan-McDermid syndrome (22q13.3 deletion syndrome). Accumulated experimental evidence demonstrates that the zebrafish model system is useful for studying the functions of ASD-related gene during early development. However, many basic features of shank3 transcript expression in zebrafish remain poorly understood. Here, we investigated temporal, spatial, and isoform-specific expression patterns of shank3 during zebrafish development on the basis of previous researches and the differential effects of each shank3 transcript expression after exposure to valproic acid (VPA), an ASD-associated drug. At first, we observed that both shank3a and shank3b were barely expressed at very early ages (before 24 h post-fertilization (hpf)), whereas their expression levels were increased and mainly enriched in the nervous system after 24 hpf. Secondly, all of the six shank3 transcripts gradually increased during the first 7 hpf and then decreased. Subsequently, they exhibited a second increasing peak between 1 month post-fertilization (mpf) and adulthood. Thirdly, VPA treatment affected the isoform-specific expression of zebrafish shank3. In particular, the mRNA expression levels of those isoforms that contain a SAM domain were significantly increased, whereas the mRNA expression level of those which contained an ANK domain but without a SAM domain was decreased. To conclude, our findings support the molecular diversity of shank3 in zebrafish and provide a molecular framework to understand the isoform-specific function of shank3 in zebrafish.
authors: Division of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
authors: Chun-Xue
authors: CX
authors: Liu
authors: Center for Translational Medicine, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
authors: Xiao-Lan
authors: XL
authors: Peng
authors: Division of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
authors: Chun-Chun
authors: CC
authors: Hu
authors: Division of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China.
authors: Chun-Yang
authors: CY
authors: Li
authors: Center for Translational Medicine, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. liq@fudan.edu.cn.
authors: Qiang
authors: Q
authors: Li
authors: Division of Child Health Care, Children's Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, China. xuxiu@shmu.edu.cn.
authors: Xiu
authors: X
authors: Xu
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000378:metabolism; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D000072417:Protein Domains; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C000607103:SHANK3 protein, zebrafish; D029961:Zebrafish Proteins; D014635:Valproic Acid
keywords: ANK and SAM domains; Autism spectrum disorder; Developmental expression; Transcript; Valproic acid; Zebrafish; shank3