ZBTB20 is required for anterior pituitary development and lactotrope specification

Dongmei Cao; Xianhua Ma; Jiao Cai; Jing Luan; An Jun Liu; Rui Yang; Yi Cao; Xiaotong Zhu; Hai Zhang; Yu Xia Chen; Yuguang Shi; Guang Xia Shi; Dajin Zou; Xuetao Cao; Michael J. Grusby; Zhifang Xie; Weiping J. Zhang

doi:10.1038/ncomms11121

ZBTB20 is required for anterior pituitary development and lactotrope specification

Dongmei Cao, Xianhua Ma, Jiao Cai, Jing Luan, An Jun Liu, Rui Yang, Yi Cao, Xiaotong Zhu, Hai Zhang, Yu Xia Chen, Yuguang Shi, Guang Xia Shi, Dajin Zou, Xuetao Cao, Michael J. Grusby, Zhifang Xie, Weiping J. Zhang

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37 Scopus citations

Abstract

The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

Original language	English (US)
Article number	11121
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms11121
State	Published - Apr 15 2016

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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@article{aa807bce2cd34dcfb8bc5a6e357c97d2,

title = "ZBTB20 is required for anterior pituitary development and lactotrope specification",

abstract = "The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.",

author = "Dongmei Cao and Xianhua Ma and Jiao Cai and Jing Luan and Liu, {An Jun} and Rui Yang and Yi Cao and Xiaotong Zhu and Hai Zhang and Chen, {Yu Xia} and Yuguang Shi and Shi, {Guang Xia} and Dajin Zou and Xuetao Cao and Grusby, {Michael J.} and Zhifang Xie and Zhang, {Weiping J.}",

note = "Funding Information: We thank Dr A. F. Parlow for providing the hormone antibodies. This work was supported by the grants from National Natural Science Foundation of China (81130084, 31201086, 31270814, and 31470759), National Key Basic Research Program (2012CB524904 and 2013CB530603) and Shanghai Natural Science Foundation (12ZR1436900).",

year = "2016",

month = apr,

day = "15",

doi = "10.1038/ncomms11121",

language = "English (US)",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

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T1 - ZBTB20 is required for anterior pituitary development and lactotrope specification

AU - Cao, Dongmei

AU - Ma, Xianhua

AU - Cai, Jiao

AU - Luan, Jing

AU - Liu, An Jun

AU - Yang, Rui

AU - Cao, Yi

AU - Zhu, Xiaotong

AU - Zhang, Hai

AU - Chen, Yu Xia

AU - Shi, Yuguang

AU - Shi, Guang Xia

AU - Zou, Dajin

AU - Cao, Xuetao

AU - Grusby, Michael J.

AU - Xie, Zhifang

AU - Zhang, Weiping J.

N1 - Funding Information: We thank Dr A. F. Parlow for providing the hormone antibodies. This work was supported by the grants from National Natural Science Foundation of China (81130084, 31201086, 31270814, and 31470759), National Key Basic Research Program (2012CB524904 and 2013CB530603) and Shanghai Natural Science Foundation (12ZR1436900).

PY - 2016/4/15

Y1 - 2016/4/15

N2 - The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

AB - The anterior pituitary harbours five distinct hormone-producing cell types, and their cellular differentiation is a highly regulated and coordinated process. Here we show that ZBTB20 is essential for anterior pituitary development and lactotrope specification in mice. In anterior pituitary, ZBTB20 is highly expressed by all the mature endocrine cell types, and to some less extent by somatolactotropes, the precursors of prolactin (PRL)-producing lactotropes. Disruption of Zbtb20 leads to anterior pituitary hypoplasia, hypopituitary dwarfism and a complete loss of mature lactotropes. In ZBTB20-null mice, although lactotrope lineage commitment is normally initiated, somatolactotropes exhibit profound defects in lineage specification and expansion. Furthermore, endogenous ZBTB20 protein binds to Prl promoter, and its knockdown decreases PRL expression and secretion in a lactotrope cell line MMQ. In addition, ZBTB20 overexpression enhances the transcriptional activity of Prl promoter in vitro. In conclusion, our findings point to ZBTB20 as a critical regulator of anterior pituitary development and lactotrope specification.

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ZBTB20 is required for anterior pituitary development and lactotrope specification

Abstract

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