Genetic Mosaic Analysis Reveals That GATA-4 Is Required for Proper Differentiation of Mouse Gastric Epithelium

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作者：

CM Jacobsen，N Narita，M Bielinska，AJ Syder，JI Gordon，DB Wilson

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摘要：

During mouse embryogenesis GATA-4 is expressed first in primitive endoderm and then in definitive endoderm derivatives, including glandular stomach and intestine. To explore the role of GATA-4 in specification of definitive gastric endoderm, we generated chimeric mice by introducing Gata4/ ES cells into ROSA26 morulae or blastocysts. In E14.5 chimeras, Gata4/ cells were represented in endoderm lining the proximal and distal stomach. These cells expressed early cytodifferentiation markers, including GATA-6 and ApoJ. However, by E18.5, only rare patches of Gata4/ epithelium were evident in the distal stomach. This heterotypic epithelium had a squamous morphology and did not express markers associated with differentiation of gastric epithelial cell lineages. Sonic Hedgehog, an endoderm-derived signaling molecule normally down-regulated in the distal stomach, was overexpressed in Gata4/ cells. We conclude that GATA-4-deficient cells have an intrinsic defect in their ability to differentiate. Similarities in the phenotypes of Gata4/ chimeras and mice with other genetically engineered mutations that affect gut development suggest that GATA-4 may be involved in the gastric epithelial response to members of the TGF-β superfamily.

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关键词：

endoderm stomach transcription factor H+, K+-ATPase sonic hedgehog

DOI：

10.1006/dbio.2001.0424

被引量：

216

年份：

2002