GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo

Author:

Morrisey Edward E.,Tang Zhihua,Sigrist Kirsten,Lu Min Min,Jiang Fang,Ip Hon S.,Parmacek Michael S.

Abstract

GATA6 belongs to a family of zinc finger transcription factors that play important roles in transducing nuclear events that regulate cellular differentiation and embryonic morphogenesis in vertebrate species. To examine the function of GATA6 during embryonic development, gene targeting was used to generate GATA6-deficient (GATA6−/−) ES cells and mice harboring a null mutation in GATA6. Differentiated embryoid bodies derived from GATA6−/− ES cells lack a covering layer of visceral endoderm and severely attenuate, or fail to express, genes encoding early and late endodermal markers, including HNF4, GATA4, α-fetoprotein (AFP), and HNF3β. Homozygous GATA6−/− mice died between embryonic day (E) 6.5 and E7.5 and exhibited a specific defect in endoderm differentiation including severely down-regulated expression of GATA4 and absence of HNF4 gene expression. Moreover, widespread programmed cell death was observed within the embryonic ectoderm of GATA6-deficient embryos, a finding also observed in HNF4-deficient embryos. Consistent with these data, forced expression of GATA6 activated the HNF4 promoter in nonendodermal cells. Finally, to examine the function of GATA6 during later embryonic development,GATA6−/−-C57BL/6 chimeric mice were generated. lacZ-taggedGATA6−/− ES cells contributed to all embryonic tissues with the exception of the endodermally derived bronchial epithelium. Taken together, these data suggest a model in which GATA6 lies upstream of HNF4 in a transcriptional cascade that regulates differentiation of the visceral endoderm. In addition, these data demonstrate that GATA6 is required for establishment of the endodermally derived bronchial epithelium.

Publisher

Cold Spring Harbor Laboratory

Subject

Developmental Biology,Genetics

Reference50 articles.

1. Mouse GATA-4: A retinoic acid-inducible GATA-binding transcription factor expressed in endodermally derived tissues and heart.;Arceci;Mol. Cell. Biol.,1993

2. Bradley A. (1987) Production and analysis of chimeric mice. Teratocarcinomas and embryonic stem cells, a practical approach (ed. E.J. Robertson), pp. 113–151. IRL Press, Oxford, UK..

3. Cytostatic Gene Therapy for Vascular Proliferative Disorders with a Constitutively Active form of the Retinoblastoma Gene Product

4. Disruption of the HNF-4 gene, expressed in visceral endoderm, leads to cell death in embryonic ectoderm and impaired gastrulation of mouse embryos.

5. The in vitro development of blastocyst-derived embryonic stem cell lines: Formation of visceral yolk sac, blood islands and myocardium.;Doetschman;J. Embryol. Exp. Morphol.,1985

Cited by 566 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3