Genetic mosaic analysis reveals that GATA-4 is required for proper differentiation of mouse gastric epithelium.
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.
Jacobsen
Christina M
CM
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Narita
Naoko
N
Bielinska
Malgorzata
M
Syder
Andrew J
AJ
Gordon
Jeffrey I
JI
Wilson
David B
DB
D000818:Animals; D002454:Cell Differentiation; D002678:Chimera / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D050991:GATA4 Transcription Factor; D005753:Gastric Mucosa / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009030:Mosaicism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors