Signaling Pathways in Neurovascular Development

Annu Rev Neurosci. 2022 Jul 8:45:87-108. doi: 10.1146/annurev-neuro-111020-102127.


During development, the central nervous system (CNS) vasculature grows to precisely meet the metabolic demands of neurons and glia. In addition, the vast majority of the CNS vasculature acquires a unique set of molecular and cellular properties-collectively referred to as the blood-brain barrier-that minimize passive diffusion of molecules between the blood and the CNS parenchyma. Both of these processes are controlled by signals emanating from neurons and glia. In this review, we describe the nature and mechanisms-of-action of these signals, with an emphasis on vascular endothelial growth factor (VEGF) and beta-catenin (canonical Wnt) signaling, the two best-understood systems that regulate CNS vascular development. We highlight foundational discoveries, interactions between different signaling systems, the integration of genetic and cell biological studies, advances that are of clinical relevance, and questions for future research.

Keywords: VEGF; Wnt; angiogenesis; beta-catenin; blood–brain barrier; circumventricular organs; mouse genetics.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier / metabolism
  • Central Nervous System
  • Vascular Endothelial Growth Factor A* / metabolism
  • Wnt Signaling Pathway* / physiology


  • Vascular Endothelial Growth Factor A