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

• DOI: 10.1083/jcb.201006114
• Publication Date: 2011-06-21T03:52:07Z
• Authors: Li Qian; Joshua D. Wythe; Jiandong Liu; Jerome Cartry; Georg Vogler; Bhagyalaxmi Mohap...; Robyn T. Otway; Yu Huang; Isabelle N. King; Marjorie Maillet; Yi Zheng; Timothy Crawley; Ouarda Taghli-Lam...; Christopher Semsa...; Sally Dunwoodie; David Winlaw; Richard P. Harvey; Diane Fatkin; Jeffrey A. Towbin; Jeffery D. Molkentin; Deepak Srivastava; Karen Ocorr; Benoit G. Bruneau; Rolf Bodmer
• Keywords: Heart development; CDC42

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.