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Gene Review

Gfra1  -  glial cell line derived neurotrophic...

Mus musculus

Synonyms: AU042498, GDNF family receptor alpha-1, GDNF receptor alpha-1, GDNFR-alpha, GDNFR-alpha-1, ...
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Disease relevance of Gfra1


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


Associations of Gfra1 with chemical compounds


Other interactions of Gfra1


Analytical, diagnostic and therapeutic context of Gfra1


  1. RET(Men2B)-transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf-/- or gfr alpha-1(-/-) mice. Rajan, I., Gestblom, C., Kapur, R.P. Pediatr. Dev. Pathol. (2001) [Pubmed]
  2. Neurturin responsiveness requires a GPI-linked receptor and the Ret receptor tyrosine kinase. Buj-Bello, A., Adu, J., Piñón, L.G., Horton, A., Thompson, J., Rosenthal, A., Chinchetru, M., Buchman, V.L., Davies, A.M. Nature (1997) [Pubmed]
  3. GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Enomoto, H., Araki, T., Jackman, A., Heuckeroth, R.O., Snider, W.D., Johnson, E.M., Milbrandt, J. Neuron (1998) [Pubmed]
  4. IB4-binding DRG neurons switch from NGF to GDNF dependence in early postnatal life. Molliver, D.C., Wright, D.E., Leitner, M.L., Parsadanian, A.S., Doster, K., Wen, D., Yan, Q., Snider, W.D. Neuron (1997) [Pubmed]
  5. Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation. Kawai, K., Iwashita, T., Murakami, H., Hiraiwa, N., Yoshiki, A., Kusakabe, M., Ono, K., Iida, K., Nakayama, A., Takahashi, M. Cancer Res. (2000) [Pubmed]
  6. Isolation of male germ-line stem cells; influence of GDNF. Hofmann, M.C., Braydich-Stolle, L., Dym, M. Dev. Biol. (2005) [Pubmed]
  7. Glial cell-line derived neurotrophic factor-mediated RET signaling regulates spermatogonial stem cell fate. Naughton, C.K., Jain, S., Strickland, A.M., Gupta, A., Milbrandt, J. Biol. Reprod. (2006) [Pubmed]
  8. Assignment of mouse Gfra1, the homologue of a new human HSCR candidate gene, to the telomeric region of mouse chromosome 19. Puliti, A., Cinti, R., Seri, M., Ceccherini, I., Romeo, G. Cytogenet. Cell Genet. (1997) [Pubmed]
  9. GFRalpha 1 is required for development of distinct subpopulations of motoneuron. Garcès, A., Haase, G., Airaksinen, M.S., Livet, J., Filippi, P., deLapeyrière, O. J. Neurosci. (2000) [Pubmed]
  10. GDNF family receptors in the embryonic and postnatal rat heart and reduced cholinergic innervation in mice hearts lacking ret or GFRalpha2. Hiltunen, J.O., Laurikainen, A., Airaksinen, M.S., Saarma, M. Dev. Dyn. (2000) [Pubmed]
  11. Cellular and developmental patterns of expression of Ret and glial cell line-derived neurotrophic factor receptor alpha mRNAs. Nosrat, C.A., Tomac, A., Hoffer, B.J., Olson, L. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1997) [Pubmed]
  12. Expression of GDNF and GFR alpha 1 in mouse taste bud cells. Takeda, M., Suzuki, Y., Obara, N., Uchida, N., Kawakoshi, K. J. Comp. Neurol. (2004) [Pubmed]
  13. Glial cell line-derived neurotrophic factor stimulates ureteric bud outgrowth and enhances survival of ureteric bud cells in vitro. Towers, P.R., Woolf, A.S., Hardman, P. Exp. Nephrol. (1998) [Pubmed]
  14. GDNF availability determines enteric neuron number by controlling precursor proliferation. Gianino, S., Grider, J.R., Cresswell, J., Enomoto, H., Heuckeroth, R.O. Development (2003) [Pubmed]
  15. GFRalpha-3, a protein related to GFRalpha-1, is expressed in developing peripheral neurons and ensheathing cells. Widenfalk, J., Tomac, A., Lindqvist, E., Hoffer, B., Olson, L. Eur. J. Neurosci. (1998) [Pubmed]
  16. Molecular cloning and expression analysis of GFR alpha-3, a novel cDNA related to GDNFR alpha and NTNR alpha. Nomoto, S., Ito, S., Yang, L.X., Kiuchi, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
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