How cell elimination sculpts the developing cortical astrocyte population - Abstract/ Project Summary Astrocytes are a major class of glial cells in the central nervous system (CNS) and have roles in neurotransmitter homeostasis, ion balance, and maintenance of the blood-brain barrier. How the brain achieves the correct number of astrocytes remains poorly understood. The establishment of proper cell numbers is vital for a healthy CNS. Cellular elimination is a mechanism various tissues employ to sculpt developing structures throughout the body. In the developing CNS, neuronal and oligodendrocyte progenitor cells undergo elimination, modulating the progenitor pool size. Later, following terminal differentiation, immature cells are eliminated to refine circuits. Despite the large body of literature describing elimination in neuronal and oligodendrocyte populations, little is known about whether astrocytes are established similarly. Evidence suggests that immature astrocytes are eliminated in the first postnatal week. Preliminary data indicates that during late postnatal development, astrocyte cell number declines. This suggests that astrocytes are eliminated to sculpt the final population, but the mechanism by which this occurs is not well understood. The goal of this proposal is to investigate cortical astrocytes undergo stage-specific elimination during the first month of postnatal development and determine the mechanism through which this occurs. Aim 1 seeks to determine the precise timing of astrocyte elimination during early postnatal development and the underlying mechanism. This will be accomplished through lineage tracing and cellular-specific ablation to determine whether microglial engulfment facilitates the elimination of astrocyte progenitor cells. Aim 2 will investigate astrocyte elimination during late postnatal development, how this sculpts the mature astrocyte population in the cortex, and whether neuronal activity influences astrocyte survival. The proposed experiments will be performed at Drexel University under the guidance of the sponsor and thesis committee. This project incorporates a training plan with specific training in experimental design, data analysis, scientific communication, and writing. In addition, the training plan incorporates career and professional development through participation in local and international meetings. The overarching goal of this pre-doctoral fellowship is to provide the training and experience needed to pursue a career as an independent researcher in developmental neurobiology.
