A unique cell population in the mouse olfactory bulb displays nuclear β‐catenin signaling during development and olfactory sensory neuron regeneration

Abstract

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 Wnt 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 Wnt signaling in the formation of OSN connections in the OB during development and regeneration.

Canonical Wnt signaling promotes the proliferation and neurogenesis of peripheral olfactory stem cells during postnatal development and adult regeneration

“…Using our newly generated Wnt signaling reporter TOPeGFP transgenic mice, the current results demonstrate that TOPeGFP is (Booker-Dwyer et al, 2008;Zaghetto et al, 2007). The differences between current and previous findings in the OE across the reporter strains are probably due to differences in the nature of the different reporter genes (eGFP vs -galactosidase) and the different integration sites of the transgenic constructs in these mouse lines.…”

“…Using Wnt reporter mice (TOPgal and BATgal), we and other groups have identified a unique subgroup of olfactory ensheathing cells in the inner olfactory nerve layer of the mouse olfactory bulb, where Wnt signaling might have important roles in olfactory axonal connections and regeneration (Booker-Dwyer et al, 2008;Zaghetto et al, 2007). However, TOPgal or BATgal signaling activity is weak or absent in the OE, probably because of inactivate integration of the reporter gene in the OE of these transgenic mice.…”

Long-Distance Interferon Signaling within the Brain Blocks Virus Spread

“…To test the role of IFN-␣/␤ signaling in virus spread, we used knockout (KO) mice lacking the IFN-␣/␤ receptor (27), a gift of A. Iwasaki (Yale University). To destroy the olfactory receptor neurons, the selective toxin methimazole (50 mg/kg of body weight) was given intraperitoneally to 129Bl/SJ adult male mice (Jackson Laboratory), as described elsewhere (28,29). Five days after olfactory neurons were eliminated, VSV was administered intranasally.…”

“…To test the hypothesis that the olfactory receptor neurons are critical for the induction of an ISG response to virus infection, we used methimazole to eliminate the olfactory neurons, as described previously (28,29). Prior to the primary experiment, we performed pilot experiments by testing different methimazole concentrations and exposures; the parameters described here resulted in the absence of detectable VSV in the olfactory bulb after intranasal inoculation, suggesting good ablation of olfactory receptor neurons.…”

Ceramide Glycosylation by Glucosylceramide Synthase Selectively Maintains the Properties of Breast Cancer Stem Cells

“…Globo-series of GSLs can mediate Wnt/␤-catenin signaling and cell functions (25,52,53). To elucidate how GSLs modulate BCSCs, a stepwise inhibition approach was employed to examine the effects of ceramide glycosylation on BCSC stemness.…”