Expression of TGF-beta type II receptors in the olfactory epithelium and their regulation in TGF-alpha transgenic mice.
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.
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY 40536-0230, USA. mgetch@pop.uky.edu
Marilyn L
ML
Getchell
Michael A
MA
Boggess
Samuel J
SJ
Pruden
Susan S
SS
Little
Shreya
S
Buch
Thomas V
TV
Getchell
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009830:Olfactory Bulb / Q000502:physiology; D051842:Olfactory Marker Protein; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D016211:Transforming Growth Factor alpha / Q000235:genetics*
D009419:Nerve Tissue Proteins; D051842:Olfactory Marker Protein; C497598:Omp protein, mouse; D018125:Receptors, Transforming Growth Factor beta; D016211:Transforming Growth Factor alpha; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II