THESIS
2019
xi, 110 pages : illustrations (some color) ; 30 cm
Abstract
Microglia are the major immune cells in the central nervous system (CNS). Apart from immune defense, microglia also play important roles in neural development and function, and tremendous efforts have been made to understand microglia development. In zebrafish, microglia are derived from two distinct waves of hematopoiesis. Embryonic microglia, originated from the primitive hematopoiesis, colonize the CNS during early development and only last through the juvenile stages. These early microglia are gradually replaced by cells generated in the definitive hematopoiesis, which constitute the major microglia population in the adulthood. The exact mechanism underlying their colonization, distinct developmental regulation, and functional significance remain unclear. Here, we firstly show that...[
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Microglia are the major immune cells in the central nervous system (CNS). Apart from immune defense, microglia also play important roles in neural development and function, and tremendous efforts have been made to understand microglia development. In zebrafish, microglia are derived from two distinct waves of hematopoiesis. Embryonic microglia, originated from the primitive hematopoiesis, colonize the CNS during early development and only last through the juvenile stages. These early microglia are gradually replaced by cells generated in the definitive hematopoiesis, which constitute the major microglia population in the adulthood. The exact mechanism underlying their colonization, distinct developmental regulation, and functional significance remain unclear. Here, we firstly show that I134-Csf1ra pathway function together with the natural occurring neuronal apoptosis to orchestrate the colonization of microglial precursors during early development. Loss-of-function of both il34 and its receptor csf1ra result in defective colonization of embryonic microglial precursors, while neuronal overexpression of il34 drives excess microglia into the CNS. Next, we demonstrate that csf1ra and csf1rb differentially regulates two waves of microglia, with a requirement of csf1ra for the primitive microglia and csf1rb for the definitive microglia. Finally, we identify two morphologically distinct groups of microglia that can be distinguished by specific markers in the adult zebrafish brain. Our works systematically elucidate the colonization, developmental regulation, and heterogeneity of distinct microglia populations throughout zebrafish development.
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