Olfactory sensory neurons (OSNs) in the nose form precise connections with neurons in the brain. However, mechanisms that account for the formation of such precise neuronal connections are incompletely understood. Recent studies implicate the function of Wnt growth factors in the formation of neuronal connections. To assess the role of Wnt signaling in the olfactory system, we examined the expression of beta-galactosidase (beta-gal) in the TOPGAL mouse, a transgenic strain in which beta-gal expression reports the activation of the canonical Writ signaling pathway. In the olfactory epithelium, no beta-gal expression was observed at any developmental stages. In the olfactory bulb (OB), beta-gal expression was observed in a population of cells located at the interface of the olfactory nerve layer and the glomerular layer. The beta-gal expression was developmentally regulated with the peak expression occurring at late embryonic and early postnatal stages and a greatly reduced expression in adulthood. Further, forced OSN regeneration and subsequent reinnervation of the OB led to a reactivation of beta-gal expression in mature animals. The temporal coincidence between the peak of beta-gal expression and formation of OSN connections, together with the spatial localization of these cells, suggests a potential role of these cells and canonical Writ signaling in the formation of OSN connections in the OB during development and regeneration. (C) 2008 Wiley Periodicals, Inc.