EAPSI: A Role for Microglia in Interhemispheric Remodeling of the Embryonic Forebrain

Kreutz Anna L, Davis CA

Investigators

Abstract

The cerebral cortex consists of two hemispheres, which are largely distinct structures, but are connected along the midline. This connection is necessary for interhemispheric communication and information integration. The interhemispheric connection is formed and remodeled early during fetal development, but how this occurs is poorly understood. One candidate cell type involved in interhemispheric remodeling is the microglial cell, the immune cell of the brain. Microglia are spatially and temporally correlated with midline development, and known to play a role in remodeling other regions of the cerebral cortex. Understanding interhemispheric remodeling will aid our understanding of communication between the two hemispheres and disorders of the corpus callosum, the structure bridging the two hemispheres. This research will be conducted in collaboration with Dr. Linda Richards, one of the world's leading experts on development of the cortical midline, at Queensland Brain Institute in Brisbane, Australia. Before the two cerebral hemispheres are fused, they are separated by a lining of leptomeningeal fibroblasts. These fibroblasts are removed during midline remodeling, but how they are eliminated is not well understood. To address this question, tissue will be immunostained for markers of leptomeningeal cells, microglial cells, and apoptotic cells. This research follows the hypothesis that microglia are involved in midline remodeling based on their temporospatial correlation and phagocytic nature. The project will assess a role for microglia along the cortical midline through immunohistochemistry by analyzing microglial phagocytosis of leptomeningeal cells, whether phagocytosed cells are apoptotic, and the morphology of phagocytic microglia. This research will provide insight into how the two cerebral hemispheres are fused, a potential novel role for microglia, and could provide an explanation for the distribution of microglia along the cortical midline. This award, under the East Asia and Pacific Summer Institutes program, supports summer research by a U.S. graduate student and is jointly funded by NSF and the Australian Academy of Science.