The development of a blood vessel network that can respond to autonomic neuronal inputs is a critical achievement during organogenesis. This system confers a functional benefit by delegating the involuntary control of vascular function to the autonomic nervous system, a phenomenon that is best illustrated by the “fight or flight response”. During the past year, we have focused on understanding the requirement of a particular cell adhesion molecule for proper co-patterning between blood vessels and neurons. Using several in vitro models, we were able to observe the timecourse for the development of vascular tubes comprised of multiple cell types. We discovered that co-patterning between vascular endothelial cells and autonomic neurons requires the presence of third cell type, vascular smooth muscle cells. Furthermore, we have identified a critical cell adhesion molecule that facilitates the interaction between these three cell types. Our studies focused on how autonomic neurons emerge from their precursors and our finding that aligning with blood vessels helps their differentiation is highly relevant for the development of new regenerative therapies for diseases of the autonomic nervous system, and ultimately for the engineering of organs with functional vascular networks.