Grant: CIHR Fellowship

During nervous system development, connections are formed between neurons that allow information to be transmitted between cells in the nervous system. Perturbations in the intricate wiring of neurons during nervous system development lead to motor, cognitive, and sensory dysfunctions. The cerebellum is a vital component in the human brain. Given the late development of the cerebellum compared to the other brain regions, the cerebellum is particularly sensitive to environmental and clinical factors that impact on growth (or cause injury) around birth. There are several neurodevelopmental disorders associated with defects in cerebellar development, including dyslexia and autism. During cerebellar development, cerebellar granule cell precursors proliferate and migrate to reach their final position. Migrating cerebellar cell precursors move forward, switch their direction or change their migration mode by choosing different signaling pathways and using physical substrates and chemical guidance cues. Neuronal migration is key to cerebellar development and requires the tight coordination of multiple steps to ensure correct cerebellar morphogenesis and development. However, the mechanisms that control neuronal migration in the cerebellum are not well understood. Here, we propose that Arhgef7 might be responsible to regulate GCP migration in the developing cerebellum. Our preliminary data demonstrate that Arhgef7-deficient mice show defect in cell migration of progenitor cells which result in a smaller and underdeveloped cerebellum. Our goal is to understand how Arhgef7 is regulated, and what are the neurological consequences of lacking Arhgef7 in the cerebellum. Our findings will contribute to the understanding of cerebellar development and shed light onto neurodevelopmental disorders.