Malformations of the atrial septum, which separates the two heart atria,are common human congenital heart defects, but the molecular mechanisms that orchestrate septation are unknown. On p. 1761, Ivan Moskowitz and co-workers investigate the relationship between cardiac progenitor (CP) specification and atrial septation in mice and find that sonic hedgehog (Shh) signalling specifies CPs for the septum outside of the atrium. The researchers report that hedgehog (Hh) signalling specifically marks CPs for the atrial septum and pulmonary artery and show, using genetic inducible fate mapping, that Hh-receiving CPs migrate from the second heart field into the atrium. CPs made unresponsive to Hh signalling migrate normally into the atrium, but populate the atrial walls rather than the septum. Conversely,constitutively activating Hh signalling leads to an enlarged septum. These findings indicate that Hh-mediated CP subspecification establishes a blueprint for septation. Finally, by demonstrating that removing Shh from pulmonary endoderm causes septal defects, the authors implicate respiratory tissue in cardiac patterning, and propose that cardiac septa and the respiratory apparatus might have co-evolved.

2009