Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species

Heart development CDC42
DOI: 10.1083/jcb.201006114 Publication Date: 2011-06-21T03:52:07Z
ABSTRACT
Unraveling the gene regulatory networks that govern development and function of mammalian heart is critical for rational design therapeutic interventions in human disease. Using Drosophila as a platform identifying novel interactions leading to disease, we found Rho-GTPase Cdc42 cooperates with cardiac transcription factor Tinman/Nkx2-5. Compound Cdc42, tinman heterozygous mutant flies exhibited impaired output altered myofibrillar architecture, adult heart–specific interference sufficient cause these same defects. We also identified K+ channels, encoded by dSUR slowpoke, potential effectors Cdc42–Tinman interaction. To determine whether Cdc42–Nkx2-5 interaction conserved heart, examined compound mice conduction system In exploring mechanism Nkx2-5 demonstrated mouse was target of, negatively regulated miR-1, which itself Tinman fly heart. conclude plays role regulating an indirect Tinman/Nkx2-5 via miR-1.
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