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

Abstract

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.

The Candidate Neuroprotective Agent Artemin Induces Autonomic Neural Dysplasia without Preventing Peripheral Nerve Dysfunction

“…The high affinity ART receptor is clearly GFRα-3, but neither a competing laboratory (Masure et al, 1999) nor our data (Figures 4, 5) corroborate a proposed low affinity ART-GFRα-1 pairing Milbrandt et al, 1998). However, it cannot be ruled out that supraphysiological ART concentrations might mediate productive signaling through other GFRα receptors, a possibility supported by the upregulation of ART in rat striatum ipsilateral to a chemical lesion (Zhou et al, 2000) and the capacity of ART gene therapy to ameliorate chemical lesions to mesencephalic dopaminergic neurons (Rosenblad et al, 2000) despite very low levels (Stover et al, 2000) or absence (Naveilhan et al, 1998;Widenfalk et al, 1998) of GFRα-3 expression at this site. Further work is needed to resolve this question.…”

Stable Methylation at Promoters Distinguishes Epiblast Stem Cells from Embryonic Stem Cells and the In Vivo Epiblasts

“…Of these, Abcb1a is a membrane transporter whereas the others are involved in development [41]. Chrna3, Cspg4, Daam2, and Gfra3 play roles in nervous system development [42][43][44][45][46], while Aebp1 is required for smooth muscle formation [47][48][49][50]. We verified the low level of DNA methylation in two different ESC lines, which contrasted with the high DNA methylation level (90%-98% methylated CpGs) in two EpiSC lines (Fig.…”

Binding of GDNF and Neurturin to Human GDNF Family Receptor α 1 and 2

“…Different groups (18)(19)(20)(21)(22) have reported the cloning of the GFRα3 receptor. The ligand for GFRα3, ART, was recently shown to bind to GFRα3 receptor and to be a survival factor for different sensory and sympathetic neurons (23).…”