This work was designed to understand how embryonic microglia precursors migration relates to global processes such as blood vessel development and neurogenesis and to decipher transcriptomic signatures governing embryonic microglia behavior. The zebrafish retina provides a precise anatomical and molecularly characterized extension of forebrain to study colonization by microglia precursors. In this study we decode the mechanism driving the process of the microglia precursors colonization of developing zebrafish retina and its role in early neurodegeneration of visual system. Transgenic live imaging studies and slbp1 mutant analysis of migrating microglia precursors into retina revealed that this migration is a step wise process depending on both retinal vasculogenesis and neurogenesis. These two key processes proceeds at the same time-scale as retinal colonization by microglia precursors. Initially microglia precursors uses emerging blood vessels system around the lens to enter the a space near basement membrane of the retina. As the wave of neurogenesis proceeds, these microglia precursors starts to migrate into retina, preferentially in neuronally differentiated neurons. Intraretinal microglia numbers decrease when retinal neurogenesis is delayed, suggesting crosstalk between early born neurons and microglia precursors. To explore microglia signaling during neurogenesis at the molecular level, we carried out a single-cell transcriptomic analysis of microglia precursors and newly matured microglia in the developing zebrafish brain.
Exam Date
2020-03-13
Degree Conferral Date
2020-04-30
Degree
Doctor of Philosophy
Degree Referral Number
38005甲第53号
Degree Conferrral Institution
Okinawa Institute of Science and Technology Graduate University
About OISTIR
Forms
Behavioral and transcriptomic analysis of embryonic microglia during colonization and degeneration of zebrafish retina
Full Text
(85.64MB)
