Cross-talk between blood vessels and neural progenitors in the developing brain

Abstract

The formation of the central nervous system (CNS) involves multiple cellular and molecular interactions between neural progenitor cells (NPCs) and blood vessels to establish extensive and complex neural networks and attract a vascular supply that support their function. In this review, we discuss studies that have performed genetic manipulations of chick, fish and mouse embryos to define the spatiotemporal roles of molecules that mediate the reciprocal regulation of NPCs and blood vessels. These experiments have highlighted core functions of NPC-expressed ligands in initiating vascular growth into and within the neural tube as well as establishing the blood-brain barrier. More recent findings have also revealed indispensable roles of blood vessels in regulating NPC expansion and eventual differentiation, and specific regional differences in the effect of angiocrine signals. Accordingly, NPCs initially stimulate blood vessel growth and maturation to nourish the brain, but blood vessels subsequently also regulate NPC behaviour to promote the formation of a sufficient number and diversity of neural cells. A greater understanding of the molecular cross-talk between NPCs and blood vessels will improve our knowledge of how the vertebrate nervous system forms and likely help in the design of novel therapies aimed at regenerating neurons and neural vasculature following CNS disease or injury.

Cell-Type-Specific Gene Expression in Developing Mouse Neocortex: Intermediate Progenitors Implicated in Axon Development

“…Radial glial progenitors are known to play essential roles in cerebral cortex vascular development ( Figure 4B ) ( Tata and Ruhrberg, 2018 ). For example, production of integrin-α v β 8 ( Itgav and Itgb8 ) by RGPs is essential for cortical vasculature development.…”

Structural and Functional Remodeling of the Brain Vasculature Following Stroke

“…Proper cell–cell communication within vascular niches of neurogenesis is crucial for regenerative mechanisms in the adult brain. Close reciprocal relationships between brain ECs and neural progenitor cells (NPCs) regulate neurogenesis in both the developing and adult brain ( Goldman and Chen, 2011 ; Licht and Keshet, 2015 ; Segarra et al, 2015 , 2018 ; Tata and Ruhrberg, 2018 ). NPCs secrete proangiogenic factors that promote brain vascularization, and brain ECs instruct NPCs to proliferate, differentiate, or remain quiescent through release of angiocrine messengers including NO, BDNF, stromal-derived factor 1, or angiopoietin 1 ( Ohab et al, 2006 ; Goldman and Chen, 2011 ).…”

Translational control in neurovascular brain development

“…Neuroepithelial cells transform into radial glia cells (RGCs), which are neural progenitors. Within the INVP, vascular patterning takes place via angiogenic sprouts, which co-develop with RGC fibres [3,9]. When vessels reach the ventricle, new branches emerge, they reverse their direction towards the pia and ultimately anastomose to form a rich capillary plexus called the periventricular vascular plexus (PVP) [9].…”