Michael Martinez ’25
Characterizing the postnatal development and maturation of mouse cerebellar microglia
Michael Martinez ’25, Biology major
Faculty Mentor: Dr. Ileana Soto Reyes, Biology
Poster Presentation: Wednesday, April 24, 1:30 – 3 p.m.
Previous studies in our laboratory found that changes in microglia morphology, phagocytic activity, and expression of developmental proteins linked to phagocytic activity during neurodegenerative conditions, precede Purkinje Cell (PC) death in a Niemann-Pick Type C disease mouse model. One of these developmental proteins is CLEC7A, a protein that is transiently expressed in microglia precursors during the early postnatal development of the mouse cerebellum. While CLEC7A is not found in healthy adult resting/homeostatic microglia, during neurodegenerative conditions the expression of this protein is significantly increased in activated microglia. In our lab, we found that in contrast to wild type (WT) mice, NPC1 mutant mice had an increased number of CLEC7A expressing microglia precursors. More recently, we have been using mice expressing EGFP under the TMEM119 promoter to determine the temporal and spatial development and maturation of CLEC7A+ precursors during the postnatal development of the cerebellum. TMEM119 is a microglia specific protein expressed by mature and homeostatic microglia, and significantly decreased in neurodegenerative associated microglia. The development of the cerebellum occurs postnatally, therefore at P1 age, few IBA1+ cells with low levels of TMEM119-EGFP were found in the primitive WT cerebella; no CLEC7A+ cells were found at this stage. However, at P4, few CLEC7A+ cells were detected in the WT cerebella particularly in the cerebellar medullar region. In P7 WT mice, CLEC7A expressing microglia precursors were highly abundant with minimal or not expression of TMEM119-EGFP in the developing white matter regions (WMR). Preliminary results are also indicating that in NPC1 deficient mice the number of microglia and CLEC7A+ precursors was significantly decreased at P7. NPC1 deficient microglia at P7 was less ramified and had higher levels of IBA1 than WT microglia, suggesting that lack of NPC1 delays microglia differentiation and proliferation at this stage when axons are actively myelinated.
