ROLE OF MYELOID CELLS IN REGULATING CEREBELLUM DEVELOPMENT

The cerebellum, commonly known as the little brain as it contains around 50% of all the brain’s neurons, plays an important role in coordinating both motor and cognitive functions due to its connectivity with different brain regions. Since it is one of the first brain regions to initiate cell differentiation and the last to fully mature, any dysfunction during the development process is associated with neurological disorders such as ataxia, intellectual disability, autism and attention deficit hyperactivity (ADHD).
While the neuroimmune role of microglial cells within the brain parenchyma has been largely investigated, the function of myeloid cells located at the brain borders is still understudied. The meningeal coverings of the brain are inhibited by myeloid cells, and they affect the development and function of different brain regions including the cerebellum. We hypothesize that myeloid cells orchestrate cerebellar development. Combining different mouse models and drug treatments, our preliminary data suggests that transient depletion of myeloid cells at birth leads to the modulation of genes linked to neuronal circuit formation and activity, which is associated with increased cerebellar activity during adulthood. Based on that, our aim is to identify the underlying mechanisms and overall long-term functional consequences. Methods such as spectral confocal microscopy, transcriptomic profiling and behavioral experiments are used to address this aim. We anticipate that our findings linking meningeal immunity and brain development will help design better preventive strategies to manage neurological disorders.