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

Shunji Jia; Fangyan Dai; Di Wu; Xia Lin; Cencan Xing; Yu Xue; Ying Wang; Mu Xiao; Wei Wu; Xin Hua Feng; Anming Meng

doi:10.1016/j.devcel.2012.03.001

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

Shunji Jia, Fangyan Dai, Di Wu, Xia Lin, Cencan Xing, Yu Xue, Ying Wang, Mu Xiao, Wei Wu, Xin Hua Feng, Anming Meng

Experimental Radiation Oncology

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1065-1078
Number of pages	14
Journal	Developmental cell
Volume	22
Issue number	5
DOIs	https://doi.org/10.1016/j.devcel.2012.03.001
State	Published - May 15 2012

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/j.devcel.2012.03.001

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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.",

author = "Shunji Jia and Fangyan Dai and Di Wu and Xia Lin and Cencan Xing and Yu Xue and Ying Wang and Mu Xiao and Wei Wu and Feng, {Xin Hua} and Anming Meng",

note = "Funding Information: We thank Drs. Edward Seto, Tse-Hua Tan, Peter ten Dijke, and Bert Vogelstein for providing constructs. We are grateful to the members of the Meng and Feng/Lin laboratories and Dr. Guisheng Zhou for helpful discussion and technical assistance. This work was financially supported by grants from the National Natural Science Foundation of China and Major Science Programs of China (2011CB943800, 30830068, 31090360, 30921004, and 2012CB966600), Natural Science Foundation of Zhejiang Province (Z2110591), and the National Institutes of Health (R01DK073932, R01AR053591, R01CA108454, and R01GM063773). ",

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T1 - Protein Phosphatase 4 Cooperates with Smads to Promote BMP Signaling in Dorsoventral Patterning of Zebrafish Embryos

AU - Jia, Shunji

AU - Dai, Fangyan

AU - Wu, Di

AU - Lin, Xia

AU - Xing, Cencan

AU - Xue, Yu

AU - Wang, Ying

AU - Xiao, Mu

AU - Wu, Wei

AU - Feng, Xin Hua

AU - Meng, Anming

N1 - Funding Information: We thank Drs. Edward Seto, Tse-Hua Tan, Peter ten Dijke, and Bert Vogelstein for providing constructs. We are grateful to the members of the Meng and Feng/Lin laboratories and Dr. Guisheng Zhou for helpful discussion and technical assistance. This work was financially supported by grants from the National Natural Science Foundation of China and Major Science Programs of China (2011CB943800, 30830068, 31090360, 30921004, and 2012CB966600), Natural Science Foundation of Zhejiang Province (Z2110591), and the National Institutes of Health (R01DK073932, R01AR053591, R01CA108454, and R01GM063773).

PY - 2012/5/15

Y1 - 2012/5/15

N2 - 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.

AB - 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.

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

Abstract

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