Deletion of Adaptor Protein ShcD Impairs Olfactory Bulb Morphology and Function.

Abstract

Shc family adaptor proteins are involved in diverse signaling pathways that regulate critical cellular functions, including proliferation, differentiation, migration, and survival. ShcD is the most recently isolated member and while previous studies have identified its prominent expression in the brain, specifically within the olfactory bulb, its physiological functions remain largely unknown. Here we report initial characterization of ShcD knockout (ShcD^KO) mice and identify structural, behavioral, and biochemical deficits associated with ShcD deletion. Specifically, ShcD^KO mice have decreased olfactory bulb weight with a corresponding reduced granule cell layer compared to controls, and defects in olfactory performance. Intriguingly, ShcD^KO mice display increased proliferation in the subventricular zone, which serves as the reservoir for neural progenitors migrating into the olfactory bulb. Supporting these cellular changes, we noted Erk2 hyperactivation in the olfactory bulb of ShcD^KO mice, and using a cultured neuron model, we also detected altered signaling of Erk5, a MAPK protein associated with neural stem cell differentiation, as well as increased p66ShcA expression, indicating a potential compensatory mechanism within the Shc family. These results uncover a possible physiological role for ShcD in neurogenesis and imply its involvement in signaling pathways that regulate stem cell maintenance and/or differentiation.