ABSTRACT
Numerous in vitro studies of neurogenesis of olfactory receptor neurons (ORNs) suggest that transforming growth factor (TGF)-beta promotes the maturation/differentiation of olfactory progenitors. We demonstrate that in vivo both mature and immature ORNs, and possibly a basal neuronal progenitor cell, express the TGF-beta type II receptor (TGF-betaRII), suggesting that these cells are targets for TGF-beta signaling. In a previous study of neurogenesis in the OE of TGF-alpha overexpressing transgenic (T) mice, we observed an apparent reduction in the expression of olfactory marker protein (OMP), a marker of terminal differentiation in ORNs in T mice compared to nontransgenic (NT) littermate controls; this was confirmed by Western blotting and immunohistochemistry. In contrast, there was no apparent difference between T and NT mice in the intensity of immunoreactivity for a neuronal marker, protein gene product 9.5. Because TGF-alpha overexpression has been reported to affect TGF-beta signaling in other epithelia, we compared the expression of the TGF-beta type II receptor (TGF-betaRII) in T and NT mice. The intensity of TGF-betaRII immunoreactivity on ORNs was substantially reduced in T compared to NT mice. Similar reductions in TGF-betaRII expression in vomeronasal receptor neurons and in other epithelia in the nasal cavity of T mice were also observed. Taken together, these results indicate that TGF-beta signaling regulates terminal differentiation of ORNs in vivo and suggest ways in which interactions between TGF-alpha and TGF-beta signaling pathways may interact in the OE.
