Neurovascular crosstalk coordinates the central nervous system development

Abstract

Purpose of the review: The synchronic development of vascular and nervous systems is orchestrated by common molecules that regulate the communication between both systems. The identification of these common guiding cues and the developmental processes regulated by neurovascular communication are slowly emerging. In this review, we describe the molecules modulating the neurovascular development and their impact in processes such as angiogenesis, neurogenesis, neuronal migration, and brain homeostasis.

Recent findings: Blood vessels not only are involved in nutrient and oxygen supply of the central nervous system (CNS) but also exert instrumental functions controlling developmental neurogenesis, CNS cytoarchitecture, and neuronal plasticity. Conversely, neurons modulate CNS vascularization and brain endothelial properties such as blood-brain barrier and vascular hyperemia.

Summary: The integration of the active role of endothelial cells in the development and maintenance of neuronal function is important to obtain a more holistic view of the CNS complexity and also to understand how the vasculature is involved in neuropathological conditions.

Figure 1

Neural tube vascularization: (a) Graphic representation of the developing perineural vascular plexus (PNVP, red) around the neural tube. Simultaneously to the closure of neural tube, starting around embryonic day (E) 8.5 in mouse, VEGF-A (light orange gradient) produced by this structure recruits angioblasts (red cells) from the adjacent presomitic mesoderm. This first neurovascular communication event constitutes the initiating proangiogenic signal triggering neural tube vasculogenesis. The ectoderm (blue) and notochord (pink) are located dorsal and ventral, respectively, to the neural tube. (b) Closer view of the neural tube during intraneural vascular plexus (INVP, red) formation. Approximately one day after the establishment of the PVNP, growing vessels stereotypically ingress into the neural tube from the pial (basal) toward the ventricular (apical) surface. A, anterior; D, dorsal; P, posterior; V, ventral; VEGF-A, vascular endothelial growth factor A.

Figure 2

Neurovascular communication during neocortex development: (a) Coronal schematic illustration of the mouse telencephalon around mouse embryonic day (E) 13.5–15.5. Tangential migration (blue arrows) of migrating interneurons, from the ganglionic eminence toward the developing neocortex, and radial migration (green arrows) of migrating pyramidal neurons toward the meningeal surface are shown. Both migration events happen in close proximity to the perineural vascular plexus (PNVP), periventricular vascular plexus (PVP), and developing cortical vasculature (all blood vessels in red). (b) Amplified view of the area shown in (a) as dashed box displaying the correlation of some neuronal and vascular development events in the neocortex. With the ingression of the PVP around E11.5 onwards, radial glia cells (RGCs, green) undergo asymmetric division and give rise to neurons and a diverse range of progenitor cells, here called as basal progenitors (light green). RGCs on the ventricular surface extend fibers that attach to the pial surface and are used as scaffold for radially migrating pyramidal neurons (orange), which they finally disperse and became mature neurons (brown) within their respective cortical layer. Tangentially migrating interneurons (blue) transit the neocortex along highly stereotypical routes in parallel with blood vessels and later radially integrate into functional interneurons (purple). Notice tip cells forming vessel sprouts in developing cortical vessels. D, dorsal; M, medial; MGE, medial ganglionic eminence; L, lateral; LGE, lateral ganglionic eminence; V, ventral.