Final Report Summary - NEUROVASCULAR LINK (Neuro-vascular communication in the neural tube during development)
Despite of being composed of different neural cell types, our central nervous system (CNS) is also composed of blood vessels. The neuro-vascular link ERC-StG project was focused on understand the b neuro-vascular communication in the neural tube during development. Interestingly, we found that spinal cord motor neurons control their own vascularization by an autocrine mechanism involving the main angiogenic factor VEGF and its trapping receptor sFlt1. When this process is deregulated motor neuron development and topological organization is impaired (Himmels et al. Nat Commun, 2017). We also showed that for efficient and proper blood vessel growth in the CNS, neuronal-derived VEGF activates the effectors of the Hippo pathway YAP/TAZ in endothelial cells. In the absence of YAP/TAZ, endothelial cells do not respond to VEGF, blood vessels growth is impaired and as a result endothelial cell specific YAP/TAZ knockout mice die embryonically (Wang et al. Dev Cell, 2017). Furthermore, our research lead to the observation that neuro-vascular communication is bi-directional and that blood vessels also regulate neurodevelopment by acting as important signaling players. Altogether, our work highlights the importance of a precise communication between developing neurons and the growing vasculature for achieving proper CNS development (Paredes et al. Dev Cell, 2018). It also opens different research avenues to further investigate the fundamental principles governing the formation of the CNS as well as the potential contribution of the identified mechanisms in pathological conditions.