The development of a blood vessel network that can respond to autonomic neuronal inputs is a critical proper organ formation and function. 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. In the past review cycle, we found that two different vascular cell types (endothelial cells and vascular smooth muscle cells) were required to drive stem cell differentiation towards a neuronal fate. In the past year, we showed that a direct cell-cell interaction between vascular smooth muscle and stem cells is required for their differentiation toward an autonomic fate. We found that this is due to a homotypic interaction between critical cell adhesion molecules expressed on the surface of both cell types. Understanding how autonomic neurons emerge from their precursors by aligning with blood vessels to drive 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.