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An Overview of Extrinsic and Intrinsic Mechanisms Involved in Astrocyte Development in the Central Nervous System.

Over the past few decades, our knowledge about the function of the central nervous system (CNS) and astrocytes has improved, and research has confirmed the key roles that astrocytes play in the physiology and pathology of the CNS. Here, we reviewed the intrinsic and extrinsic mechanisms that regulate the development of astrocytes, which are generated from radial glial cells (RGCs). These regulatory systems modulate various signaling pathways and transcription factors. In this review, four stages of astrocyte development -specification (patterning and switch), migration, proliferation, and maturation are discussed. In astrocyte patterning, VA1-VA3 domains create the astrocyte subtypes by differential expression of Slit1 and Reelin in the spinal cord. In the brain, patterning creates several astrocyte subtypes by different organizing centers. At the switch step, the JAK-STAT pathway governs the transition of neurogenesis to gliogenesis. BMP and Notch pathways are also important players of the pro-gliogenic switch. Intrinsic regulation is mediated by DNA methylation transferases (DnmTs) and polycomb group complexes (PcG) can intrinsically affect the development of astrocytes. In the next stage, these cells proliferate and migrate to their final location. Astrocyte maturation is accomplished through the development of cellular processes, molecular markers, and functions.