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Astrocytes  - Development and Stem Cells


Anatomical Structure and Function of the Astrocytes:

Astrocytes, a sub-type of glia, are the most abundant cells in the mammalian central nervous system (CNS) and play numerous roles in the CNS, including provision of structural support, contribution to the blood brain barrier, ion balance maintenance, synaptic regulation and enhancement of myelination by oligodendrocytes. They are also involved in repair and formation of glial scars following traumatic injuries.

Astrocytes are categorized into two subpopulations based on their location and morphology: protoplasmic astrocytes located in the grey matter and fibrous astrocytes which can be found in the white matter. Protoplasmic astrocytes generally express S100b, and feature many branching processes, which envelop synapses and whose endfeet cover blood vessels. Fibrous astrocytes express GFAP, and have unbranched cylindrical processes that align with myelinated fibers, generating an elongated morphology. Astrocytes in the gray matter are typically larger than white matter astrocytes.

Bergmann glia in the cerebellum and Muller glia in the retina are two types of specialized CNS radial astroglia, both of which are morphologically similar to radial glia. In the development, Bergmann glia, like radial glia, serve as a scaffold for migrating neurons. In the adult CNS, Bergmann glia and Muller glia functionally resemble protoplasmic astrocytes in their modulation of synaptic function.

Embryonic and Postnatal Development of the Astrocytes:

All CNS neurons and glia (astrocytes and oligodendrocytes) are generated from radial glia cells in the ventricular zone and subventricular zone, the walls of the embryonic neural tube. Astrogenesis begins after neurogenesis and peaks in various rodent CNS regions during the late prenatal to early postnatal stages (E18-P7).

During development, the main sources of astrocytes are brain and spinal cord radial glia. In the adult, astrocytes remain capable of mitosis and give rise to differentiated astrocytes. In response to injury, they rapidly divide to form a glial scar in both the brain and spinal cord. Astrocytes can also arise from adult neural stem cells at the cortical subventricular zone in the walls of the lateral ventricles. In the LifeMap database, astrocytes originating from the cerebral cortex and the spinal cord, where gliogenesis is most commonly studied, are mapped.

In the developing spinal cord, the p1, p2 and p3 ventral progenitor domains, appearing around E12.5, give rise to VA1, VA2 and VA3 fibrous astrocyte subpopulations in the spinal cord white matter. Astrocytes are also generated from Dbx+ progenitor cells located in the dP5 and dP6 dorsal spinal cord domains.

In the developing cerebral cortex, astrocyte precursor cells arise from radial glia within the cortical subventricular zone, which give rise to both protoplasmic and fibrous astrocytes located in the grey matter and white matter, respectively.

To date, little is known about astrocyte development and heterogeneity. Markers that can reliably identify subsets of astrocytes have only recently been identified.