title: Setdb2 controls convergence and extension movements during zebrafish gastrulation by transcriptional regulation of dvr1.
abstract: As the primary driving forces of gastrulation, convergence and extension (C&E) movements lead to a medio-lateral narrowing and an anterior-posterior elongation of the embryonic body axis. Histone methylation as a post-translational modification plays a critical role in early embryonic development, but its functions in C&E movements remain largely unknown. Here, we show that the setdb2-dvr1 transcriptional cascade plays a critical role in C&E movements during zebrafish gastrulation. Knockdown of Setdb2, a SET domain-containing protein possessing a potential histone H3K9 methyltransferase activity, induced abnormal C&E movements, resulting in anterior-posterior shortening and medio-lateral expansion of the embryonic axis, as well as abnormal notochord cell polarity. Furthermore, we found that Setdb2 functions through fine-tuning the expression of dvr1, a ligand of the TGF-β superfamily, to an appropriate level to ensure proper C&E movements in a non-cell-autonomous manner. In addition, both overexpression and knockdown of Dvr1 at the one-cell stage resulted in defects at epiboly and C&E. These data demonstrate that Setdb2 is a novel regulator for C&E movements and acts by modulating the expression level of dvr1, suggesting that Dvr1 acts as a direct and essential mediator for C&E cell movements.
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Du
authors.affiliation: Department of Cell Biology, University of Virginia, Charlottesville, VA, USA.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Xu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Dong
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Fan
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Pan
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rui-Bao
authors.initials: RB
authors.lastname: Ren
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Ting-Xi
authors.initials: TX
authors.lastname: Liu
authors.affiliation: Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China. Electronic address: mdeng@sibs.ac.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Deng
authors.affiliation: State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: HQH10632@rjh.com.cn.
authors.forename: Qiu-Hua
authors.initials: QH
authors.lastname: Huang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D054262:Gastrulation / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D055785:Gene Knockdown Techniques; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism / Q000502:physiology*; D017403:In Situ Hybridization; D046228:Microarray Analysis; D060172:Morpholinos / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: C079678:Gdf3 protein, zebrafish; D060172:Morpholinos; D016212:Transforming Growth Factor beta; D029961:Zebrafish Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C549064:Setdb2 protein, zebrafish
keywords: Convergence and extension; Dvr1; Histone methylation; Setdb2; TGF-β superfamily; Zebrafish