Axon behavior in the olfactory nerve reflects the involvement of catenin-cadherin mediated adhesion

Abstract

The projection of olfactory sensory neuron (OSN) axons to the olfactory bulb (OB) is a complex but well-regulated process. Although odorant receptor proteins, and other molecules, are implicated in this process, our understanding remains incomplete. We demonstrate that axons remain restricted to the outer olfactory nerve layer (ONLo) until they are proximal to their target glomeruli, where they enter the inner ONL (ONLi), dividing the ONL into extension and sorting zones. Sorting is likely contingent on cell:cell interactions mediated in part by cell adhesion molecules. The cadherins are a large family of adhesion molecules whose function is contingent on their intracellular binding partners, the catenins, which in turn link to the cytoskeleton. We previously demonstrated that the organization of the cytoskeleton changed as olfactory sensory neuron axons moved from the ONLo to the ONLi. To further assess the role of cadherin mediated adhesion in the developing mouse ONL, we localized alpha-, beta-, gamma-, delta-, and p120-catenins as well as neural cadherin (N-cadherin; CDH2) in the OB. alpha- and beta-catenins are found throughout the OB and are uniform throughout the ONL. In contrast, gamma-catenin and CDH2 are expressed predominantly in the ONLo during perinatal development, but are uniform across the ONL beginning at P7 and into adulthood. Finally, p120- and delta-catenins are expressed in nonoverlapping patterns by olfactory axons and OB neuronal dendrites, respectively. We conclude that gamma-catenin-mediated CDH2 adhesion may influence OSN targeting by restricting axons to the ONLo until they reach the appropriate domain of the OB.