Disease relevance of Gfra1

• A relevant clinical question is whether ablation of either GDNF or GFR alpha-1 could alter penetrance or severity of the MEN2B syndrome [1].

High impact information on Gfra1

• GDNF signals through a receptor complex consisting of the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor termed GDNFR-alpha [2].
• These results suggest that while stringent physiologic pairing exists between GFR alpha1 and GDNF in renal and enteric nervous system development, significant cross-talk between GDNF and other GFR alpha coreceptors must occur in other neuronal populations [3].
• Ret-expressing neurons also express the glycosyl-phosphatidyl inositol-linked (GPI-linked) GDNF binding component GDNFR-alpha and retrogradely transport 125I-GDNF, indicating the presence of a biologically active GDNF receptor complex [4].
• Because these tissues but not tumors expressed glial cell line-derived neurotrophic factor family receptor alpha (GFR alpha) at high levels, this suggested that GFR alpha expression may interfere in the dimerization of the RET-MEN2A mutant proteins, leading to tissue-specific tumor development in vivo [5].
• This report describes the first isolation of a pure population of GFR alpha-1-positive cells in the testis and identifies signaling pathways that may play a crucial role in maintaining germ-line stem cell proliferation and/or renewal [6].

Biological context of Gfra1

• We used the whole-testis transplantation technique to overcome the limitation of neonatal lethality of Gdnf-, Gfra1-, and Ret-deficient mice and found that each of these genes is required for postnatal spermatogenesis and not for embryological testes development [7].
• Assignment of mouse Gfra1, the homologue of a new human HSCR candidate gene, to the telomeric region of mouse chromosome 19 [8].
• During their natural programmed cell death period, motoneurons in the Gfra1(-/-) mutant mice undertook increased apoptosis [9].
• In accordance with the phenotype of the mutant motoneurons observed in culture we found the loss of distinct groups of motoneurons, identified by several markers, in the Gfra1(-/-) spinal cords but no gross defects in the Gfra2(-/-) mutant [9].
• We report that ganglioneuromatous tumors caused by a RET(Men2B) transgene in mice are not affected grossly or microscopically by the absence of gdnf or gfr alpha-1 [1].

Anatomical context of Gfra1

• Gfra1 was expressed in the endocardial cushion mesenchyme at E12 and later, in the developing and mature valves, and in the walls of the aorta and the pulmonary trunk [10].
• Using specific PCR primers on a somatic cell hybrid mapping panel and fluorescence in situ hybridization with an expressed sequence tag (EST) cDNA clone corresponding to the mouse Gfra1, we mapped the gene to mouse chromosome 19D2-D3, a region with known homology with human chromosome 10q24-->q26 [8].
• In the kidney and the gastrointestinal tract, GDNFR-alpha mRNA and Ret mRNA distribution overlapped [11].
• Expression of GDNF and GFR alpha 1 in mouse taste bud cells [12].
• Here we describe expression studies of ret, GDNF, and a co-receptor for GDNF (GDNFR alpha) in the developing mouse metanephros, lung, and submandibular salivary gland [13].

Associations of Gfra1 with chemical compounds

• GDNFR-alpha mRNA was strongly expressed in the developing and adult dopamine neurons [11].

Other interactions of Gfra1

• Only mild reductions in neuron size and neuronal fiber counts occur in Ret(+/-) and Gfra1(+/-) mice [14].
• 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 [15].

Analytical, diagnostic and therapeutic context of Gfra1

• Molecular cloning and expression analysis of GFR alpha-3, a novel cDNA related to GDNFR alpha and NTNR alpha [16].

References