Immunohistochemical expression of two members of the GDNF family of growth factors and their receptors in the olfactory system

Abstract

The glial cell line-derived (GDNF) family of trophic factors, GDNF, neurturin, persephin and artemin, are known to support the survival and regulate differentiation of many neuronal populations, including peripheral autonomic, enteric and sensory neurons. Members of this family of related ligands bind to specific GDNF family receptor (GFR) proteins, which complex and signal through the Ret receptor tyrosine kinase. We showed previously that GDNF protein was detectable in olfactory sensory neurons (OSNs) in the olfactory neuroepithelium (ON). In this immunohistochemical study, we localized GDNF, neurturin, GFRalpha1, GFRalpha2 and Ret in the adult rat ON and olfactory bulb. We found that GDNF and Ret were widely expressed by immature and mature OSNs, while neurturin was selectively expressed in a subpopulation of OSNs zonally restricted in the ON. The GFRs had differential expression, with mature OSNs and their axons preferentially expressing GFRalpha1, whereas progenitors and immature neurons more avidly expressed GFRalpha2. In the bulb, GDNF was highly expressed by the mitral and tufted cells, and by periglomerular cells, and its distribution generally resembled that of Ret, with the exception that Ret was far more predominant on fibers than cell bodies. Neurturin, in contrast, was present at lower levels and was more restricted in its expression to the axonal compartment. GFRalpha2 appeared to be the dominant accessory protein in the bulb. These data are supportive of two members of this neurotrophic family, GDNF and neurturin, playing different physiological roles in the olfactory neuronal system.

Critical Role of GFRα1 in the Development and Function of the Main Olfactory System

“…Our findings of the cell types expressing GFRα1 in the main olfactory system contrast with an earlier study that reported GFRα1 expression throughout the whole OE of the adult rat, predominantly in layers corresponding to mature OSNs, and also in OB glomeruli (Maroldt et al, 2005). However, the authors of that report did not perform colocalization studies with either GAP-43 or OMP to precisely localize the GFRα1 signal within the OE, nor with any OB markers.…”

“…The OE and OB undergo simultaneous but independent developmental programs during the early formation of the main olfactory system. Expression of GDNF, GFRα1, and RET has been detected in both the OE and OB (Choi-Lundberg and Bohn, 1995; Nosrat et al, 1997; Trupp et al, 1997; Maroldt et al, 2005), but the specific cellular localization of these proteins has not been elucidated. More importantly, despite the abundant expression of these components, the physiological role of GDNF signaling in the olfactory system has not been investigated and remains completely unknown.…”

The fine-structural distribution of G-protein receptor kinase 3, β-arrestin-2, Ca2+/calmodulin-dependent protein kinase II and phosphodiesterase PDE1C2, and a Cl−-cotransporter in rodent olfactory epithelia

“…The fact that olfactory epithelial sensory and supporting cells share several proteins, as found here, thought to be specific for receptor cells (or more general, for neurons) extends to several proteins thought to be neuronspecific (forthcoming articles in these series: Maroldt et al, 2005: Weiler & Benali, 2005. This reinforces the notion of a common origin of both cells (see Discussion, first part).…”