Research Grant Award

Research Fellowship Award

Riccomagno, Martin M., PhD

The Johns Hopkins School of Medicine, Baltimore, MD
P130Cas in granule cell migration: understanding the mechanisms underlying cell migration in cerebellar development

Non-progressive congenital ataxias represent a genetically heterogeneous group of neurological disorders. Several of these ataxias are caused by defects of the cerebellum, a region of the brain in charge of balance and coordination of motor functions. Some of these defects may be caused by an embryonic developmental deficit. A key step during cerebellar development is the inward migration of a certain type of neuron, the granule cells, from the external granule cell layer (EGL) to the internal granule cell layer (IGL). This migration is tightly regulated by signaling cues that are known to attract and repel cells and axons. Previous data suggests that a cytoplasmic protein, p130Cas, may be required for some of these signaling cues to be able to instruct cerebellar cells to move. However, little is known about Cas protein function in neuronal migration and cerebellar development. The objective of this proposal is to define and characterize the function of vertebrate Cas proteins in granule cell migration and axon guidance. To achieve this objective we will take different approaches, including the generation of a mouse deficient for p130Cas, which may serve as a model for developmentally caused ataxias.