Crosstalk between Blood Vessels and Glia during the Central Nervous System Development

The formation of proper blood vessel patterns in the central nervous system (CNS) is crucial to deliver oxygen and nutrient to neurons efficiently. At the same time, neurons must be isolated from the outer blood circulation by a specialized structure, the blood-brain barrier (BBB), to maintain the microenvironment of brain parenchyma for the survival of neurons and proper synaptic transmission. To develop this highly organized structure, glial cells, a major component of the brain, have been reported to play essential roles. In this review, the crosstalk between the macroglia, including astrocytes and oligodendrocytes, and endothelial cells during the development of CNS will be discussed. First, the known roles of astrocytes in neuro-vascular unit and its development, and then, the requirements of astrocytes for BBB development and maintenance are shown. Then, various genetic and cellular studies revealing the roles of astrocytes in the growth of blood vessels by providing a scaffold, including laminins and fibronectin, as well as by secreting trophic factors, including vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) are introduced. Finally, the interactions between oligodendrocyte progenitors and blood vessels are overviewed. Although these studies revealed the necessity for proper communication between glia and endothelial cells for CNS development, our knowledge about the detailed cellular and molecular mechanisms for them is still limited. The questions to be clarified in the future are also discussed.