Expression of TGF-β type II receptors in the olfactory epithelium and their regulation in TGF-α transgenic mice

Abstract

Numerous in vitro studies of neurogenesis of olfactory receptor neurons (ORNs) suggest that transforming growth factor (TGF)-β 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-β type II receptor (TGF-βRII), suggesting that these cells are targets for TGF-β signaling. In a previous study of neurogenesis in the OE of TGF-α 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-α overexpression has been reported to affect TGF-β signaling in other epithelia, we compared the expression of the TGF-β type II receptor (TGF-βRII) in T and NT mice. The intensity of TGF-βRII immunoreactivity on ORNs was substantially reduced in T compared to NT mice. Similar reductions in TGF-βRII 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-β signaling regulates terminal differentiation of ORNs in vivo and suggest ways in which interactions between TGF-α and TGF-β signaling pathways may interact in the OE.