Molecular Pathways and Heart Development

Owen WJ Prall, Mary K Menon, Mark J Solloway, Yusuke Watanabe, Stéphane Zaffran, Fanny Bajolle, Christine Biben, Jim J McBride, Bronwyn R Robertson, Hervé Chaulet, Fiona A Stennard, Natalie Wise, Daniel Schaft, Orit Wolstein, Milena B Furtado, Hidetaka Shiratori,6 Kenneth R Chien, Hiroshi Hamada,6 Brian L Black, Yumiko Saga, Elizabeth J Robertson, Margaret E Buckingham, and Richard P Harvey. An Nkx2-5/Bmp2/Smad1 negative feedback loop controls second heart field progenitor specification and proliferation. Cell. 2007 March 9; 128(5): 947–959. doi: 10.1016/j.cell.2007.01.042.

Summary: During heart development the second heart field (SHF) provides progenitor cells for most cardiomyocytes and expresses the homeodomain factor Nkx2-5. We now show that feedback repression of Bmp2/Smad1 signaling by Nkx2-5 critically regulates SHF proliferation and outflow tract (OFT) morphology. In the cardiac fields of Nkx2-5 mutants, genes controlling cardiac specification (including Bmp2) and maintenance of the progenitor state were up-regulated, leading initially to progenitor over-specification, but subsequently to failed SHF proliferation and OFT truncation. In Smad1 mutants, SHF proliferation and deployment to the OFT were increased, while Smad1 deletion in Nkx2-5 mutants rescued SHF proliferation and OFT development. In Nkx2-5 hypomorphic mice, which recapitulate human congenital heart disease (CHD), OFT anomalies were also rescued by Smad1 deletion. Our findings demonstrate that Nkx2-5 orchestrates the transition between periods of cardiac induction, progenitor proliferation and OFT morphogenesis via a Smad1-dependent negative feedback loop, which may be a frequent molecular target in CHD.

...goat anti-Isl1, raised against full length human Isl1, GT15051, Neuromics)...