GFRalpha-3, a protein related to GFRalpha-1, is expressed in developing peripheral neurons and ensheathing cells

We report here the identification of a gene, termed GFRalpha-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), related to GFRalpha-1 and GFRalpha-2 (also known as GDNFR-alpha and GDNFR-beta), and describe distribution of GDNFalpha-3 in the nervous system and other parts of the mouse body during development and in the adult. GFRalpha-3 in situ hybridization signals were found mainly in the peripheral nervous system, with prominent signals in developing dorsal root and trigeminal ganglia. Sympathetic ganglia were also positive. Developing nerves manifested strong GFRalpha-3 mRNA signals, presumably generated by the Schwann cells. Olfactory ensheathing cells were also positive. Other non-neuronal cells appearing positive during development included chromaffin cells in the adrenal gland and small clusters of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with the present probes. Compared with the previously described GFRalpha-1 and GFRalpha-2 mRNAs, which are widely distributed in the central nervous system and peripheral organs, the expression of GFRalpha-3 mRNA is much more restricted. The prominent expression in Schwann cells during development suggests a key role for GFRalpha-3 in the development of the peripheral nervous system. As Schwann cells are known to lack expression of the transducing RET receptor, we propose that a possible function of GFRalpha-3 during development could be to bind Schwann cell-derived GDNF-like ligands, thus presenting such molecules to growing axons.