Protein Phosphatase 4 Cooperates with Smads to Promote BMP Signaling in Dorsoventral Patterning of Zebrafish Embryos
- Authors
- Jia, S., Dai, F., Wu, D., Lin, X., Xing, C., Xue, Y., Wang, Y., Xiao, M., Wu, W., Feng, X.H., and Meng, A.
- ID
- ZDB-PUB-120522-11
- Date
- 2012
- Source
- Developmental Cell 22(5): 1065-1078 (Journal)
- Registered Authors
- Jia, Shunji, Meng, Anming, Wu, Di, Xing, Cencan
- Keywords
- none
- MeSH Terms
-
- Smad1 Protein/metabolism*
- Animals, Genetically Modified
- Body Patterning/physiology*
- Phosphoprotein Phosphatases/genetics
- Phosphoprotein Phosphatases/metabolism*
- Signal Transduction
- Inhibitor of Differentiation Protein 1/metabolism
- Zebrafish Proteins/metabolism*
- Chromatin Immunoprecipitation/methods
- Bone Morphogenetic Proteins/metabolism*
- Cell Line, Tumor
- Bone Morphogenetic Protein 2/metabolism
- Humans
- Mice
- Zebrafish/embryology*
- Zebrafish/genetics
- Animals
- Smad5 Protein/metabolism*
- HEK293 Cells
- PubMed
- 22595677 Full text @ Dev. Cell
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.