University of Southern California

Sucov Lab

USC Stem Cell

Coronary vasculogenesis in development and regeneration

Coronary vasculogenesis requires CXCL12 signaling. Hearts were retroaortically perfused with ink to visualize the coronary stems (co) and the extent of vascular development. Coronary ostia that are patent for blood flow form in mutants but quickly degenerate into a poorly differentiated plexus, although a small number of functional vessels do form (arrowhead). Mutant embryos die in late gestation because of vascular insufficiency. From Cavallero et al., 2015.

Coronary vasculogenesis requires CXCL12 signaling. Hearts were retroaortically perfused with ink to visualize the coronary stems (co) and the extent of vascular development. Coronary ostia that are patent for blood flow form in mutants but quickly degenerate into a poorly differentiated plexus, although a small number of functional vessels do form (arrowhead). Mutant embryos die in late gestation because of vascular insufficiency. From Cavallero et al., 2015.

Coronary blood vessels form to nourish the heart as it becomes bigger and stronger in development. We identified CXCL12 as an epicardial factor that is selectively required for coronary vasculogenesis (Cavallero et al., 2015). Cxcl12 or Tie2Cre/Cxcr4 conditional mutants form an initial coronary vascular plexus, which then fails to remodel into a hierarchical network of mature vessels (see the figure). CXCL12 is therefore a new factor that controls the maturation of an initially immature vascular plexus. Interestingly, only the heart and a small number of other organs appear to utilize CXCL12 in their vasculogenic program, and the conditions that account for this specificity are under active investigation. We also have an interest in seeing if CXCL12 signaling is required for neonatal heart regeneration and its role in adult heart regeneration. Both themes stem from the concept that efficient heart regeneration at any stage will require not only cardiomyocyte regeneration but also regrowth of a coronary vascular supply.