Abstract

GATA binding protein 6 (GATA6) is a transcription factor that is expressed in the early blastocyst stage and controls the expression of important genes in the differentiation and development of the heart, pancreas, and intestine. This study confirmed the role of GATA6 in cell differentiation and or- gan development using mouse embryonic stem cells and zebrafish, respectively. First, the mouse em- bryonic stem cells were differentiated into pacemaker cardiomyocytes. An RT-PCR analysis revealed that the expression of the GATA6 gene was greatly increased from day 4 of differentiation. The ex- pression of GATA6 was upregulated prior to increased expression of NK2 homeobox 5 (Nkx2.5) and myocyte enhancer factor 2C (MEF2C), which are critical transcription factors involved in regulating heart formation. To examine the role of GATA6 in development, GATA6 morpholino was micro- injected into zebrafish embryos. Knockdown of GATA6 expression significantly decreased the heart size and heart rate in the zebrafish compared to a control. In addition, the brains were degenerated in the GATA6 morpholino-injected zebrafish. Acridine orange staining showed that knockdown of GATA6 expression increased apoptotic cells in the brain. Interestingly, knockdown of GATA6 ex- pression decreased apoptotic cells in the early bud stage. This study points to the importance of the GATA6 gene in heart and brain development.

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