Despite the critical importance of a precisely formed vascular network within the central nervous system (CNS), little is known about the molecular mechanisms that specifically control CNS vascularization. While other embryonic tissues undergo primary vascularization, the CNS becomes secondarily vascularized by sprouting angiogenesis from a previously formed vascular plexus. Angiogenesis within the CNS seems to require a different code of angiogenic signals compared to other organs, as surprisingly newly formed blood vessels avoid CNS regions where the pro-angiogenic factor VEGF is expressed. Still, angiogenesis within the developing neural tube (NT) follows a highly stereotypic pattern with blood vessels sprouting always at the same locations, following the same paths and avoiding specific regions.The goal of this project is to elucidate the cellular and molecular mechanisms that control this specialized two-step CNS vascularization.The originality and innovative character of this proposal relates to the hypothesis that in contrast to primary vascularization, which happens in response to conventional angiogenic signals, NT vascularization occurs by an orchestration of neuronal-derived signals, guiding vessels into the developing CNS, thereby assuring synchrony and adaptation to the specialized CNS tissue.Two research tracks are proposed:1: Identification of the neuronal cell populations that communicate with blood vessels during NT vascularization2: Identification and functional characterization of the molecular players controlling vascular patterning within the NTBoth tracks are designed to follow a multidisciplinary approach combining cutting edge technology in in vitro cell and 3D tissue culture, time-lapse microscopy, transcriptomics, proteomics and mouse genetics.This project will provide fundamental knowledge on the mechanisms of CNS vascularization and open new research lines for understanding and treating developmental and traumatic CNS disorders