Abstract:

Title:

The role of axonal guidance proteins in neurodevelopment and disease.

Drs. Giger and Murphy are investigating the role that members of the Semaphorin (SEMA) family of axon guidance molecules, and their receptors, the Plexins (PLXN) play in neurodevelopment and how mutant forms of these proteins might contribute to mental illness, in particular schizophrenia. Previous work from the Giger/Murphy labs has demonstrated that in mice genetic ablation of PlxnA2 results in severe malformation of the dentate gyrus which is associated with deficits in associative learning, sociability, and sensorimotor gating-traits commonly observed in neuropsychiatric disorder (PMID: 29320740). Current work is focused on extending these observations using regionally restricted and cell type specific deletion of PlxnA2 as well as targeted disruption of the GTPase-activating protein (GAP) domain in the PlxnA2 cytoplasmic region. Proteomics-based approaches are used to characterize the “interactome” of the Sema/Plxn receptor complex. These studies will be complemented by electrophysiological recordings, histological analyses and high- resolution magnetic resonance imaging.