The role of Extracellular Vesicles during CNS development

With a diverse set of neuronal and glial cell populations, Central Nervous System (CNS) has one of the most complex structures in the body. Intercellular communication is therefore highly important to coordinate cell-to-cell interactions. Besides electrical and chemical messengers, CNS cells also benefit from another communication route, what is known as extracellular vesicles, to harmonize their interactions. Extracellular Vesicles (EVs) and their subtype exosomes are membranous particles secreted by cells and contain information packaged in the form of biomolecules such as small fragments of DNA, lipids, miRNAs, mRNAs, and proteins. They are able to efficiently drive changes upon their arrival to recipient cells. EVs actively participate in all stages of CNS development by stimulating neural cell proliferation, differentiation, synaptic formation, and mediating reciprocal interactions between neurons and oligodendrocyte for myelination process. Researchers from Maastricht University discuss the presence and contribution of EVs at each CNS developmental milestone.

Schematic of exosome secretion, structure, and involvement during CNS development

The exosome cargos are sorted into early endosomes through either endocytosis, inward folding of plasma membrane, or directly from Golgi network, a process that is mediated by the endosomal sorting complexes required for transport (ESCRT) machinery. Invagination of the late endosomes, also referred as Multivesicular bodies (MVBs), forms intraluminal vesicles (ILVs). These ILVs are eventually released as exosomes into extracellular space by fusion of MVBs with plasma membrane. The precise mechanism of release is not clear however, intracellular calcium and depolarization, mediated by glutamatergic synaptic activity, are indicated as triggers for exosome secretion. Some of the exosome contents are highlighted at each stages of CNS development. As it is shown, miRNAs are the most studied element of exosomes during neuro-gliogenesis. CAM kinase II alpha is suggested as one of the candidate cargos of synaptic exosome, a scenario which needs to be investigated. Interestingly, exosomes actively involve in myelination mainly by transporting myelin related proteins between neurons and oligodendrocytes.