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PMID: 9832509 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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

Genes & development ·Vol. 12 ·No. 22 ·1998-11-15 ·Pages 3579-90

Morrisey EE, Tang Z, Sigrist K, Lu MM, Jiang F, Ip HS, Parmacek MS

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, alpha-fetoprotein (AFP), and HNF3beta. 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-tagged GATA6(-/-) 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.

MeSH Terms
3T3 Cells Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cell Differentiation/genetics DNA-Binding Proteins/genetics Embryo, Mammalian/pathology Embryonic and Fetal Development/genetics Endoderm/cytology GATA6 Transcription Factor Gene Expression Regulation, Developmental/genetics Gene Targeting Genotype Hepatocyte Nuclear Factor 4 Histocytochemistry In Situ Hybridization Lung/embryology Mice Mice, Knockout Microscopy, Electron Phosphoproteins/genetics RNA, Messenger/genetics Transcription Factors/genetics Transcriptional Activation/genetics Viscera/growth & development
Chemicals
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors DNA-Binding Proteins GATA6 Transcription Factor Gata6 protein, mouse Hepatocyte Nuclear Factor 4 Phosphoproteins RNA, Messenger Tcfl4 protein, mouse Transcription Factors
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Morrisey E E
Department of Medicine, University of Chicago, Chicago, Illinois 60637 USA.
Tang Z
Sigrist K
Lu M M
Jiang F
Ip H S
Parmacek M S
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.12.22.3579
Published
1998-11-15
Pages
3579-90
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC317242
Subset
IM
Grants
NHLBI NIH HHS · HL51145 · United States
External Links
PubMed source DOI: 10.1101/gad.12.22.3579 PMC Full Text View journal details
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