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

Dev Biol. 2002 Jan 1;241(1):34-46. doi: 10.1006/dbio.2001.0424.

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(-/-) 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-beta superfamily.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation
  • Chimera / genetics
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Epithelium / embryology
  • Epithelium / growth & development
  • Epithelium / metabolism
  • GATA4 Transcription Factor
  • Gastric Mucosa / embryology*
  • Gastric Mucosa / growth & development*
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation, Developmental
  • Hedgehog Proteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mosaicism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Trans-Activators / genetics
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • GATA4 Transcription Factor
  • Hedgehog Proteins
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors