A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain.

Abstract

Although topographical maps organize many peripheral sensory systems, mouse olfactory sensory neurons (OSNs) are thought to randomly choose which one of ∼1,100 possible olfactory receptors (ORs) to express, with spatial organization in the olfactory epithelium limited to a handful of broad anatomical "zones" that modestly restrict OR choice. Here, we reveal that each OR is instead expressed at a unique mean dorsoventral position, thereby instantiating a stereotyped receptor map in the olfactory epithelium. OSN dorsoventral identities are encoded by a coherent gene expression program, which includes key transcription factors and axon guidance molecules; use of this program reflects a dorsoventral gradient in retinoic acid signaling, translates each physical location into a spatially appropriate distribution of potential OR choices, and aligns receptor maps in the nose and brain. Spatial order in the olfactory system, therefore, arises from a continuously varying transcriptional code that precisely organizes the many discrete channels responsible for smell.