Protein Phosphatase 4 Cooperates with Smads to Promote BMP Signaling in Dorsoventral Patterning of Zebrafish Embryos

• DOI: 10.1016/j.devcel.2012.03.001
• Publication Date: 2012-05-14T16:19:06Z
• Authors: Shunji Jia; Fangyan Dai; Di Wu; Xia Lin; Cencan Xing; Yu Xue; Ying Wang; Mu Xiao; Wei Wu; Xin-Hua Feng; Anming Meng
• Keywords: Inhibitor of Differentiation Protein 1; Smad5 Protein; Chromatin Immunoprecipitation; 0303 health sciences; Bone Morphogenetic Protein 2; Zebrafish Proteins; Smad1 Protein; Animals, Genetically Modified; Mice; 03 medical and health sciences; HEK293 Cells; Cell Line, Tumor; Bone Morphogenetic Proteins; Phosphoprotein Phosphatases; Animals; Humans; Zebrafish; Developmental Biology; Body Patterning; Signal Transduction

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.