Neurovesicles in Brain Development

Abstract

Long before the nervous system is organized into electrically active neural circuits, connectivity emerges between cells of the developing brain through extracellular signals. Extracellular vesicles that shuttle RNA, proteins, and lipids from donor cells to recipient cells are candidates for mediating connectivity in the brain. Despite the abundance of extracellular vesicles during brain development, evidence for their physiological functions is only beginning to materialize. Here, we review evidence of the existence, content, and functions of extracellular vesicles in brain development.

Keywords: Exosome; Extracellular vesicle; Microvesicle; Nanovesicle; Neural stem cell; Neurovesicle.

Fig. 1

Schematic of extracellular vesicles (EVs) and cortical development. a During formation of the neural tube at embryonic day eight (E8), invagination of the epithelium results in neuroepithelial stem cells (NESCs) that orient their apical surface toward the lumen of the neural tube. NESCs contain CD133 on the ventricular projecting primary cilia, mid-body, and microvilli. NESCs release CD133 positive large ~600 nm, (P2 fraction; pink) and 50–80 nm (P4 fraction; blue) vesicles into the lumen of the neural tube. b NESCs produce choroid plexus epithelial cells (CPEs) beginning at E11−12. Cultured CPEs release extracellular vesicles including microvesicles (MV, green). c At E11−12, radial glia are generated from NESCs, and span the developing cortex, beginning at the ventricular surface and extending a radial process to the pial surface. It is unknown whether EVs are released from radial glia. d Radial glia undergo asymmetric division and give rise to immature glutamatergic neurons, called neuroblasts, that migrate into and populate the cortical plate. Through a similar process, neuroblasts that are produced in the developing chick embryo delaminate from the ventricular surface and release a particle into the ventricle during apical abscission (Apical Abscission Particle; purple). e Once neuroblasts mature into neurons, excitatory stimuli such as glutamate and depolarization can induce the release of microvesicles (green) and exosomes (red) that may target astrocytes while others target neurons. Oligodendrocytes that myelinate the axons of neurons also release EVs in response to glutamate. f NESCs eventually give rise to astrocytes which release EVs that target neurons. As with oligodendrocyte EVs, those from astrocytes seem to be neurotrophic. g NSCs that persist in the subventricular zone (SVZ) are contiguous with the lateral ventricles. SVZ NSCs generate both exosomes (red) and microvesicles (green)