Molecular and functional investigation of Polycomb Group proteins and their involvement in olfactory neurogenesis

Abstract

One of the main features of the mammalian olfactory system is the singular expression of the receptors responsible for detection of odorous stimuli, known as ORs: each olfactory sensory neuron expresses only one out of a thousand OR receptor gene candidates. The molecular mechanisms underlying this process remain one of the great mysteries of the nervous system. Recent publications suggest the involvement of epigenetic modifications in this process, though experiments proving a causal relationship between epigenetic regulation and singular expression of ORs are still lacking. Several molecular components take part in the control of gene expression through chromatin modifications, including histone modifying enzymes. Among these, members of the Polycomb Group (PcG) are of special significance and known to act in chromatin remodeling accompanying gene expression during differentiation of several cell types. In the current project, we will study the expression profile of PcG genes in the mouse olfactory epithelium, not just spatially, but also temporally and quantitatively. Furthermore, we will perform experiments to establish a possible participation of such components on the mechanisms that control the singularity of receptor expression in olfactory neurons. We expect that this proposal will bring invaluable data for the better understanding of the the sensory systems, particularly on the role of PcG proteins in the molecular bases of the intriguing process of olfactory receptor gene expression.