[PhD Thesis Presentation] ‐ Ms. Nishtha Ranawat – “Embryonic microglia migration into zebrafish retina and changes in transcriptome therein”

     Microglia are the tissue resident macrophages of the brain that play critical role in establishment and maintenance of neuro-immunological interactions from early embryonic stages to adult life. The developing zebrafish retina provides a precise anatomical and molecularly characterized region of the forebrain ideal for studying migration of embryonic microglia. In this study we explored mechanisms underlying the colonization of developing zebrafish retina by microglia precursors. We also characterized microglia behavior in the context of retinal neurodegeneration. Migration of microglia precursors into retina was mainly studied using live imaging of transgenic fish and mutant fish models. Quantitative image analysis revealed that migration of microglia is a stepwise process depending on retinal blood vessel development followed by retinal neurogenesis. Initially, microglia precursors use emerging blood vessel system surrounding the lens to enter the space near basement membrane of retina. Thereafter, with propagation of waves of neurogenesis, these precursors begin to position themselves into neural retina with clear preferences towards regions that have undergone differentiation over undifferentiated ones. Furthermore, a significant reduction of microglia population is observed in delayed neurogenesis mutant. This suggests a possibility of molecular crosstalk between early born retinal neurons and embryonic microglia, thereby influencing microglia content within the retina. Lastly, with the help of single cell transcriptome analysis, we attempted to characterize microglia at the molecular level mainly focusing on targets/pathways contributing to migration into neural regions.