title: Regulator of G protein signaling 2 (Rgs2) regulates neural crest development through Pparδ-Sox10 cascade.
abstract: Neural crest cells are multipotent progenitors that migrate extensively and differentiate into numerous derivatives. The developmental plasticity and migratory ability of neural crest cells render them an attractive model for studying numerous aspects of cell progression. We observed that zebrafish rgs2 was expressed in neural crest cells. Disrupting Rgs2 expression by using a dominant negative rgs2 construct or rgs2 morpholinos reduced GTPase-activating protein activity, induced the formation of neural crest progenitors, increased the proliferation of nonectomesenchymal neural crest cells, and inhibited the formation of ectomesenchymal neural crest derivatives. The transcription of pparda (which encodes Pparδ, a Wnt-activated transcription factor) was upregulated in Rgs2-deficient embryos, and Pparδ inhibition using a selective antagonist in the Rgs2-deficient embryos repaired neural crest defects. Our results clarify the mechanism through which the Rgs2-Pparδ cascade regulates neural crest development; specifically, Pparδ directly binds to the promoter and upregulates the transcription of the neural crest specifier sox10. This study reveals a unique regulatory mechanism, the Rgs2-Pparδ-Sox10 signaling cascade, and defines a key molecular regulator, Rgs2, in neural crest development.
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1 Road, Taoyuan, Taiwan.
authors.forename: Sheng-Jia
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Department of Life Science, College of Science and Engineering, Fu Jen Catholic University, New Taipei City, Taiwan.
authors.forename: Ming-Chang
authors.initials: MC
authors.lastname: Chiang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1 Road, Taoyuan, Taiwan.
authors.forename: Hung-Yu
authors.initials: HY
authors.lastname: Shih
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung City, Taiwan.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.affiliation: Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Section of Movement Disorders, Department of Neurology, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan.
authors.forename: Tu-Hsueh
authors.initials: TH
authors.lastname: Yeh
authors.affiliation: College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan.
authors.forename: Yin-Cheng
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1 Road, Taoyuan, Taiwan.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1 Road, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital at Linkou Medical Center, Taoyuan, Taiwan. Electronic address: yccheng@mail.cgu.edu.tw.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Cheng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D009432:Neural Crest / Q000254:growth & development / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics*; D047494:PPAR delta / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D015027:Zebrafish / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D047494:PPAR delta; D020710:RGS Proteins; D055757:SOXE Transcription Factors; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C442229:sox10 protein, zebrafish
keywords: Neural crest; Pparδ; Rgs2; Sox10; Zebrafish