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• W1839443055 abstract "textabstractDifferent members of the GAT A family of transcription factors havebeen studied extensively in our lab. The role of GAT A-I in the differentiationof erythroid blood cells and of GATA-3 during T-lymphocyte development aretwo typical examples. GATA-6 is the most recently characterized member ofthe family. Based on its expression pattern during mouse embryonicdevelopmentfor a role for GATA-6 in cardiogenesis had been speculated.To investigate what role GATA-6 may play during embryogenesis weused targeted inactivation of the gene in Embryonic Stem (ES) cells (chapter2). Unexpectedly, homozygote mutant embryos die just after implantation atembryonic day 5.5. Generation of chimeric embryos in which the GATA-6mutant cell population was confmed in either the embryo or to theextraembryonic tissues revealed that the primary defect in GATA-6 nullembryos lies in an extraembryonic cell lineage. Further in vivo and in vitroanalysis of the mutant embryos suggested that the affected lineage is thevisceral yolk sac endoderm, a derivative of the primitive endoderm.Cardiogenesis could not be directly studied since mutant embryos diewell before heart development starts (embryonic day 8.5). However, inchimeric embryos, GATA-6 -/- ES cells give rise to cardiomyocytes inapparently normal hearts, possibly due to redundant functions with the coexpressedGATA-4 and -5. In contrast, GATA-6 is the only member of thefamily that is expressed in the lung endoderm. Following on a publishedobservation showing no contribution of GATA-6 null ES cells to the lungepithelium, we decided to generate more highly chimeric embryos to analyzethe development of the lung, which is a derivative of another endodermlineage, the definitive endoderm (chapter 3). Surprisingly, we found that lungendoderm can be formed from GATA-6 mutant cells. However, this mutantendoderm has subsequent morphogenetic and differentiation defects.The importance of GATA-6 protein levels during lung developmentwas confirmed by a different approach. The gene was overexpressed intransgenic mice with a pulmonary epithelium specific promoter (chapter 4).High levels of the protein resulted in branching defects and more interestinglyin a block oflung endoderm differentiation to distal alveolar epithelium." @default.
• W1839443055 created "2016-06-24" @default.
• W1839443055 creator A5037301829 @default.
• W1839443055 date "2001-04-25" @default.
• W1839443055 modified "2023-09-24" @default.
• W1839443055 title "The role ofthe transcription factor GATA-6 in mouse embryonic development" @default.
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