Defects in the heart and/or blood vessels (cardiovascular defects) in both humans and mice can result from mutations in any one of a number of genes encoding proteins that are part of the Notch signaling cascade. However, it has not been determined which cell type these mutations affect to cause these cardiovascular defects.
In a study that appears in the February issue of the Journal of Clinical Investigation, Jonathan Epstein and colleagues from the University of Pennsylvania, Philadelphia, show that mice in which the Notch signaling cascade is only inhibited in cells of the neural crest lineage (which includes both smooth and skeletal muscle cells) develop cardiovascular defects. Further analysis showed that during cardiac development the Notch signaling cascade is active in the developing vascular smooth muscle cells and that when this signaling cascade is inhibited few cells express markers of developing vascular smooth muscle cells. Consistent with this, inhibition of the Notch signaling cascade in neural crest cells in vitro prevented them from differentiating into smooth muscle cells. This study therefore identifies cells of the neural crest lineage as the cells in which Notch signaling is important for cardiovascular development in mice and might provide a cellular mechanism for the cardiovascular defects observed in humans with the hereditary disorder Alagille syndrome, which has been linked to mutations in genes encoding proteins that are part of the Notch signaling cascade.
In an accompanying commentary, Leonard Anderson and Gary Gibbons from the Morehouse School of Medicine, Atlanta, discuss the intriguing possibility that defects in the Notch signaling cascade might also be important in adult vascular diseases; something that Epstein and colleagues also suggest.
- « Novartis :: HIV/AIDS advocates protest Novartis’ case challenge India Patent Law
- Multiple Sclerosis :: Stress response prevents neurodegeneration »
Sub-editorHeart :: NOTCHing up heart development
by Sub-editor ( Author at Spirit India )
Posted on February 2nd, 2007 at 11:27 pm.
Find more from SpiritIndia on: Health