Renewal and Differentiation of GCD Necklace Olfactory Sensory Neurons

Abstract

Both canonical olfactory sensory neurons (OSNs) and sensory neurons belonging to the guanylate cyclase D (GCD) "necklace" subsystem are housed in the main olfactory epithelium, which is continuously bombarded by toxins, pathogens, and debris from the outside world. Canonical OSNs address this challenge, in part, by undergoing renewal through neurogenesis; however, it is not clear whether GCD OSNs also continuously regenerate and, if so, whether newborn GCD precursors follow a similar developmental trajectory to that taken by canonical OSNs. Here, we demonstrate that GCD OSNs are born throughout adulthood and can persist in the epithelium for several months. Phosphodiesterase 2A is upregulated early in the differentiation process, followed by the sequential downregulation of β-tubulin and the upregulation of CART protein. The GCD and MS4A receptors that confer sensory responses upon GCD neurons are initially expressed midway through this process but become most highly expressed once CART levels are maximal late in GCD OSN development. GCD OSN maturation is accompanied by a horizontal migration of neurons toward the central, curved portions of the cul-de-sac regions where necklace cells are concentrated. These findings demonstrate that-like their canonical counterparts-GCD OSNs undergo continuous renewal and define a GCD-specific developmental trajectory linking neurogenesis, maturation, and migration.

Keywords: MS4A; adult neurogenesis; guanylate cyclase D; main olfactory epithelium; necklace olfactory system; neuronal migration; neuronal regeneration.