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Title: The role of GRIM-19 in xenopus embryo development
Authors: CHEN YONG
Keywords: mitochondrial complex I; GRIM-19; NFTA; heart development; Xenopus laevis
Issue Date: 18-Jul-2007
Citation: CHEN YONG (2007-07-18). The role of GRIM-19 in xenopus embryo development. ScholarBank@NUS Repository.
Abstract: Mitochondrial respiratory chain (MRC) plays crucial roles in cellular energy production. However, its function in the early embryonic development remains largely unknown. To investigate this issue, GRIM-19, a newly identified MRC complex I subunit, was knocked down in Xenopus embryos. Severe deficiency in heart development was observed with suppressed expression or activity of several genes involved in cardiogenesis including Nkx2.5 and NFAT. Additional studies show that disruption of the expression of GRIM19 or NDUFS3, another complex I subunit protein, resulted in impairing intracellular calcium signaling which in turn compromised the activity of NFATs, calcium- calcineurin-dependent transcription factors. Furthermore, NFAT was shown to directly regulate Nkx2.5 transcription by binding on Nkx2.5 promoter. Our data therefore demonstrate that an intact and functional MRC is necessary for the normal heart development in Xenopus by controlling the intracellular calcium signaling pathways and the subsequent activation of NFAT(s) which is essential for regulation the expression of key transcription factor Nkx2.5 during cardiogenesis.
Appears in Collections:Ph.D Theses (Open)

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