GATA6 regulates HNF4 and is required for differentiation of visceral endoderm in the mouse embryo
AUTOR(ES)
Morrisey, Edward E.
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
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-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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=317242Documentos Relacionados
- Expression of transcription factor HNF-4 in the extraembryonic endoderm, gut, and nephrogenic tissue of the developing mouse embryo: HNF-4 is a marker for primary endoderm in the implanting blastocyst.
- Gata5 is required for the development of the heart and endoderm in zebrafish
- BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo
- Sox7 Plays Crucial Roles in Parietal Endoderm Differentiation in F9 Embryonal Carcinoma Cells through Regulating Gata-4 and Gata-6 Expression
- Bmp4 is required for the generation of primordial germ cells in the mouse embryo