생명과학회지 (Journal of Life Science)

  • 제25권11호
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  • Pages.1230-1234
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  • 2015
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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심장과 뇌 발달에서 GATA6 유전자 발현 감소가 미치는 영향

The Effects of the Expression of GATA Binding Protein 6 on Heart and Brain Development

  • 투고 : 2015.10.10
  • 심사 : 2015.11.10
  • 발행 : 2015.11.30
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초록

GATA binding protein 6 (GATA6)는 초기 배반포 단계에서 발현이 시작되어, 심장, 췌장, 장 등의 분화와 발달에 중요한 유전자 발현을 조절하는 전사인자이다. 본 연구에서는 GATA6의 세포 분화와 개체 발달 과정에서의 역할을 마우스 배아줄기세포와 zebrafish를 이용하여 확인하였다. 먼저, 마우스 배아줄기세포를 박동하는 pacemaker 심근세포로 분화 유도하였다. RT-PCR을 실시하여 심근세포 분화 과정에서 GATA6 유전자 발현 변화를 확인한 결과, Gata6의 발현이 분화 4일째부터 증가함을 확인하였다. GATA6 유전자의 발현 증가는 심장 발달에 필수적인 전사인자인 NK2 homeobox 5 (Nkx2.5)나 myocyte enhancer factor 2C (MEF2C)의 발현 증가에 앞서 나타났다. GATA6 유전자가 발달 과정에 미치는 영향을 확인하기 위하여 GATA6의 morpholino를 zebrafish 배아에 microinjection하여 발생 변화를 관찰하였다. GATA6의 발현을 knockdown시킨 zebrafish의 심장은 크기가 감소하였고, 심박동률 또한 감소하였다. 한편, 뇌에서는 전체적인 뇌 퇴행이 관찰되었는데, acridine orange로 염색 한 결과, 뇌 전체에서의 세포사멸의 증가를 나타내었다. 흥미롭게도, GATA6의 발현 감소는 초기 bud 단계에서는 오히려 세포사멸을 감소시켰다. 본 연구는 심장과 뇌 발달에서의 GATA6 유전자의 중요성을 시사한다.

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 organ development using mouse embryonic stem cells and zebrafish, respectively. First, the mouse embryonic 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 expression 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 microinjected 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 expression 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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