Genetic mosaic analysis reveals that GATA-4 is required for proper differentiation of mouse gastric epithelium

Christina M. Jacobsen, Naoko Narita, Malgorzata Bielinska, Andrew J. Syder, Jeffrey I. Gordon, David B. Wilson

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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-l- 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.

Original languageEnglish
Pages (from-to)34-46
Number of pages13
JournalDevelopmental Biology
Volume241
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • Endoderm
  • H, K-ATPase
  • Sonic hedgehog
  • Stomach
  • Transcription factor

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