GFR-ALPHA-3, A PROTEIN RELATED TO GFR-ALPHA-1, IS EXPRESSED IN DEVELOPING PERIPHERAL NEURONS AND ENSHEATHING CELLS

We report here the identification of a gene, termed GFR alpha-3 (glial cell line-derived neurotrophic factor family receptor alpha-3), relat ed to GFR alpha-1 and GFR alpha-3 (also known as GDNFR-alpha and GDNFR -beta), and describe distribution of GDNF alpha-3 in the nervous syste m and other parts of the mouse body duping development and in the adul t. GFR alpha-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 GFR alpha-3 mRNA signals, presumab ly generated by the Schwann cells. Olfactory ensheathing cells were al so positive. Other non-neuronal cells appearing positive during develo pment included chromaffin cells in the adrenal gland and small cluster s of cells in the intestinal epithelium. In the central nervous system no robust signals could be detected at any stage investigated with th e present probes. Compared with the previously described GFR alpha-1 a nd GFR alpha-2 mRNAs, which are widely distributed in the central nerv ous system and peripheral organs, the expression of GFR alpha-3 mRNA i s much more restricted. The prominent expression in Schwann cells duri ng development suggests a key role for GFR alpha-3 in the development of the peripheral nervous system. As Schwann cells are known to lack e xpression of the transducing RET receptor, we propose that a possible function of GFR alpha-3 during development could be to bind Schwann ce ll-derived GDNF-like ligands, thus presenting such molecules to growin g axons.