The role ofthe transcription factor GATA-6 in mouse embryonic development
Year: 2001
Type: dissertation
Abstract: Different members of the GAT A family of transcription factors have\\nbeen studied extensively in our lab. The role of GAT A-I in the differentiation\\nof erythroid blood cells and of GATA-3 during T-lymphocyte development are\\ntwo typical examples. GATA-6 is the most recently characterized member of\\nthe family. Based on its expression pattern during mouse embryonic\\ndevelopmentfor a role for GATA-6 in cardiogenesis had been speculated.\\nTo investigate what role GATA-6 may play during embryogenesis we\\nused targeted inactivation of the gene in Embryonic Stem (ES) cells (chapter\\n2). Unexpectedly, homozygote mutant embryos die just after implantation at\\nembryonic day 5.5. Generation of chimeric embryos in which the GATA-6\\nmutant cell population was confmed in either the embryo or to the\\nextraembryonic tissues revealed that the primary defect in GATA-6 null\\nembryos lies in an extraembryonic cell lineage. Further in vivo and in vitro\\nanalysis of the mutant embryos suggested that the affected lineage is the\\nvisceral yolk sac endoderm, a derivative of the primitive endoderm.\\nCardiogenesis could not be directly studied since mutant embryos die\\nwell before heart development starts (embryonic day 8.5). However, in\\nchimeric embryos, GATA-6 -/- ES cells give rise to cardiomyocytes in\\napparently normal hearts, possibly due to redundant functions with the coexpressed\\nGATA-4 and -5. In contrast, GATA-6 is the only member of the\\nfamily that is expressed in the lung endoderm. Following on a published\\nobservation showing no contribution of GATA-6 null ES cells to the lung\\nepithelium, we decided to generate more highly chimeric embryos to analyze\\nthe development of the lung, which is a derivative of another endoderm\\nlineage, the definitive endoderm (chapter 3). Surprisingly, we found that lung\\nendoderm can be formed from GATA-6 mutant cells. However, this mutant\\nendoderm has subsequent morphogenetic and differentiation defects.\\nThe importance of GATA-6 protein levels during lung development\\nwas confirmed by a different approach. The gene was overexpressed in\\ntransgenic mice with a pulmonary epithelium specific promoter (chapter 4).\\nHigh levels of the protein resulted in branching defects and more interestingly\\nin a block oflung endoderm differentiation to distal alveolar epithelium.
Author: Manousos Koutsourakis
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1839443055