{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T03:12:17Z","timestamp":1789355537883,"version":"build-2803163510"},"reference-count":63,"publisher":"The Company of Biologists","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1995,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Transcription factor GATA-4 belongs to a family of zinc finger proteins involved in lineage determination. GATA-4 is first expressed in yolk sac endoderm of the developing mouse and later in cardiac tissue, gut epithelium and gonads. To delineate the role of this transcription factor in differentiation and early development, we studied embryoid bodies derived from mouse embryonic stem (ES) cells in which both copies of the Gata4 gene were disrupted. Light and electron microscopy demonstrated that embryoid bodies formed from wild-type and heterozygous deficient ES cells were covered with a layer of visceral yolk sac endoderm, whereas no yolk sac endoderm was evident on the surface of the homozygous deficient embryoid bodies. Independently selected homozygous deficient cell lines displayed this distinctive phenotype, suggesting that it was not an artifact of clonal variation. Biochemical markers of visceral endoderm formation, such as \u03b1-feto-protein, hepatocyte nuclear factor-4 and binding sites for Dolichos biflorus agglutinin, were absent from the homozygous deficient embryoid bodies. Examination of other differentiation markers in the mutant embryoid bodies, studies of ES cell-derived teratocarcinomas and chimeric mouse analysis demonstrated that GATA-4-deficient ES cells have the capacity to differentiate along other lineages. We conclude that, under in vitro conditions, disruption of the Gata4 gene results in a specific block in visceral endoderm formation. These homozygous deficient cells should yield insights into the regulation of yolk sac endoderm development and the factors expressed by visceral endoderm that influence differentiation of adjoining ectoderm\/mesoderm.<\/jats:p>","DOI":"10.1242\/dev.121.11.3877","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T02:13:38Z","timestamp":1619403218000},"page":"3877-3888","source":"Crossref","is-referenced-by-count":223,"title":["Targeted mutagenesis of the transcription factor GATA-4 gene in mouse embryonic stem cells disrupts visceral endoderm differentiation in vitro"],"prefix":"10.1242","volume":"121","author":[{"given":"Claire","family":"Soudais","sequence":"first","affiliation":[{"name":"University of Chicago School of Medicine 1 Departments of Medicine , , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Bielinska","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 6 Departments of Pediatrics , , St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markku","family":"Heikinheimo","sequence":"additional","affiliation":[{"name":"University of Helsinki 5 Children\u2019s Hospital , , Helsinki, Finland"},{"name":"Washington University School of Medicine 6 Departments of Pediatrics , , St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig A.","family":"MacArthur","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 6 Departments of Pediatrics , , St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Narita","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 6 Departments of Pediatrics , , St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey E.","family":"Saffitz","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 7 Departments of Pathology , , St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Celeste","family":"Simon","sequence":"additional","affiliation":[{"name":"University of Chicago School of Medicine 2 Molecular Genetics and Cell Biology , , Chicago, IL, USA"},{"name":"The Howard Hughes Medical Institute 4 , University of Chicago School of Medicine, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Leiden","sequence":"additional","affiliation":[{"name":"University of Chicago School of Medicine 1 Departments of Medicine , , Chicago, IL, USA"},{"name":"University of Chicago School of Medicine 3 Pathology , , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine 6 Departments of Pediatrics , , St Louis, MO 63110, USA"},{"name":"Washington University School of Medicine 8 Departments of Molecular Biology and Pharmacology , , St Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[1995,11,1]]},"reference":[{"key":"2025011515174640700_DEVELOP_121_11_3877C1","first-page":"2235","article-title":"Mouse GATA-4: a retinoic acid-inducible GATA-binding transcription factor expressed in endodermal derivatives and heart","volume":"13","author":"Arceci","year":"1993","journal-title":"Mol. 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