Julia Carson ’25
Effects of CLEC7A Deficiency in Cerebellar Microglia Development
Julia Carson ’25, Biology major
Faculty Mentor: Dr. Ileana Soto Reyes
Oral Presentation: Wednesday, April 24, 10 a.m.
Proliferative region-associated microglia (PAM) are a subpopulation of microglia found specifically in the white matter region (WMR) of the brain during developmental stages. A group of genes were identified as highly expressed by this type of microglia and includes Clec7a, Spp1, and Apoe among others. In previous studies, using CLEC7A immunoreactivity, we found that the number of CLEC7A+ microglia was increased in the postnatal cerebellar WMR of mutant NPC1 mice, a model of the lysosomal storage diseases Niemann-Pick Type C disease. We have been using CLEC7A deficient mice to investigate the role of this protein in the differentiation and maturation of microglial cells during the postnatal development of the cerebellum. Our preliminary results showed that at postnatal day 7 (P7), when myelination is occurring, the number of WMR microglia was decreased in CLEC7A deficient mice when compared to wild-type (WT) mice. The morphology of CLEC7A deficient microglia was not different from WT cells. To identify PAM cells in the cerebellum of P7 CLEC7A deficient mice, probes for Spp1 and Apoe were used to perform RNAscope experiments. Interestingly, in the WT and CLEC7A KO mice, not all the PAM cells were double positive for Spp1 and Apoe, in fact, the majority of Spp1+ cells had lower levels of Apoe expression. We also found that the number of Spp1+ PAM cells was significantly reduced in CLEC7A deficient mice when compared to WT mice. Also, the fluorescence intensity of Spp1 and Apoe was decreased in CLEC7A deficient mice. Overall, our results suggest that the lack of CLEC7A in microglia alters the proliferation and expression of genes characteristic of PAM cells.