title: Protein phosphatase 4 cooperates with Smads to promote BMP signaling in dorsoventral patterning of zebrafish embryos.
abstract: BMP signals play pivotal roles in dorsoventral patterning of vertebrate embryos. The role of Ppp4c, the catalytic subunit of ubiquitous protein phosphatase 4, in vertebrate embryonic development and underlying mechanisms is poorly understood. Here, we demonstrate that knockdown of zebrafish ppp4cb and/or ppp4ca inhibits ventral development in embryos and also blocks ventralizing activity of ectopic Smad5. Biochemical analyses reveal that Ppp4c is a direct binding partner and transcriptional coactivator of Smad1/Smad5. In response to BMP, Ppp4c is recruited to the Smad1-occupied promoter, and its phosphatase activity is essential in inhibiting HDAC3 activity and, consequently, potentiating transcriptional activation. Consistently, genetic or chemical interference of Hdac3 expression or activity compromises the dorsalizing phenotype induced by ppp4cb knockdown. We conclude that Ppp4c is a critical positive regulator of BMP/Smad signaling during embryonic dorsoventral pattern formation in zebrafish.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Shunji
authors.initials: S
authors.lastname: Jia
authors.forename: Fangyan
authors.initials: F
authors.lastname: Dai
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Xia
authors.initials: X
authors.lastname: Lin
authors.forename: Cencan
authors.initials: C
authors.lastname: Xing
authors.forename: Yu
authors.initials: Y
authors.lastname: Xue
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Mu
authors.initials: M
authors.lastname: Xiao
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Feng
authors.forename: Anming
authors.initials: A
authors.lastname: Meng
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000378:metabolism; D051379:Mice; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism*; D051902:Smad5 Protein / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D051798:Inhibitor of Differentiation Protein 1; D051898:Smad1 Protein; D051902:Smad5 Protein; D029961:Zebrafish Proteins; C497801:smad5 protein, zebrafish; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4