Separating genetic and hemodynamic defects in neuropilin 1

Abstract

Formation of the cardiovascular system is crucial for embryo growth and survival and the importance of proper blood flow even during these early stages is becoming increasingly clear. In recent years, there has been a debate regarding which aspects of early vascular formation are genetically predetermined, and which are governed by external stimuli, such as mechanical and biochemical signaling. Though the initial vascular network is patterned without knowledge of the functional requirements, it makes biological sense that a feedback mechanism with respect to physiological function would set in as soon as this information becomes available. We recently showed that physical forces created by blood flow are necessary for proper vascular development and remodeling. In this study, we show how to distinguish between genetic defects and biomechanical defects during vascular development. Using mouse embryo culture, we study hemodynamic defects in Nrp1−/− mice together with an analysis of the emerging vascular defects. The geometry of yolk sac blood vessels is altered and remodeling into yolk sac arteries and veins does not occur. To separate flow‐induced deficiencies from those caused by the nrp‐1 mutation, we arrested blood flow in cultured wild‐type and mutant embryos and followed their vascular development. This method allows genetic defects caused by loss‐of‐function of a gene important for cardiovascular development to be isolated even in the presence of hemodynamic defects.Grant Funding SourceNSERC