Abstract
Microglia are resident immune cells in the central nervous system, showing a regular distribution. Advancing microscopy and image processing techniques have contributed to elucidating microglia’s morphology, dynamics, and distribution. However, the mechanism underlying the regular distribution of microglia remains to be elucidated. First, we quantitatively confirmed the regularity of the distribution pattern of microglial soma in the retina. Second, we formulated a mathematical model that includes factors that may influence regular distribution. Next, we experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). The resulting model simulation from the measured parameters showed that direct cell–cell contact is most important in generating regular cell spacing. Finally, we tried to specify the molecular pathway responsible for the repulsion between neighboring microglia.
Highlights
Microglia are resident immune cells in the central nervous system, showing a regular distribution
We used the P5 mouse retina to observe microglia in both vascular and avascular areas since that microglia are associated with developing vasculature[4]
Microglia are already present in all regions of the embryonic day 11.5 (E11.5) mouse retina[24], and angiogenesis starts at birth from the center but does not reach the retinal edges at P 525
Summary
Microglia are resident immune cells in the central nervous system, showing a regular distribution. We experimentally quantified the model parameters (cell movement, process formation, and ATP dynamics). Microglia are derived from primitive hematopoiesis progenitors in the fetal yolk sac during the early embryonic stage[12, 13] They migrate into all CNS regions, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype[14]. We tried to elucidate the mechanism of regular distribution formation using the mouse retina as a model system. To verify the models experimentally, we quantified the model parameters, reproduced the dynamics with numerical simulations, and tried to specify the molecular pathway responsible for the repulsion between neighboring microglia
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