• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of embojLink to Publisher's site
EMBO J. Mar 17, 1997; 16(6): 1258–1267.
PMCID: PMC1169724

Shared and distinct functions of RAGS and ELF-1 in guiding retinal axons.


Two ligands for Eph-related receptor tyrosine kinases, RAGS and ELF-1, have been implicated in the control of development of the retinotectal projection. Both molecules are expressed in overlapping gradients in the tectum, the target area of retinal ganglion cell axons. In two in vitro assays ELF-1 is shown to have a repellent axon guidance function for temporal, but apparently not for nasal axons. RAGS on the other hand is repellent for both types of axons, though to different degrees. Thus, RAGS and ELF-1 share some and differ in other properties. The biological activities of these molecules correlate with the strength of interaction with their receptors expressed on RGC axons. The meaning of these findings for guidance of retinal axons in the tectum is discussed.

Full Text

The Full Text of this article is available as a PDF (692K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Beckmann MP, Cerretti DP, Baum P, Vanden Bos T, James L, Farrah T, Kozlosky C, Hollingsworth T, Shilling H, Maraskovsky E, et al. Molecular characterization of a family of ligands for eph-related tyrosine kinase receptors. EMBO J. 1994 Aug 15;13(16):3757–3762. [PMC free article] [PubMed]
  • Bennett BD, Zeigler FC, Gu Q, Fendly B, Goddard AD, Gillett N, Matthews W. Molecular cloning of a ligand for the EPH-related receptor protein-tyrosine kinase Htk. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1866–1870. [PMC free article] [PubMed]
  • Bergemann AD, Cheng HJ, Brambilla R, Klein R, Flanagan JG. ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites. Mol Cell Biol. 1995 Sep;15(9):4921–4929. [PMC free article] [PubMed]
  • Brambilla R, Klein R. Telling axons where to grow: a role for Eph receptor tyrosine kinases in guidance. Mol Cell Neurosci. 1995 Dec;6(6):487–495. [PubMed]
  • Brambilla R, Schnapp A, Casagranda F, Labrador JP, Bergemann AD, Flanagan JG, Pasquale EB, Klein R. Membrane-bound LERK2 ligand can signal through three different Eph-related receptor tyrosine kinases. EMBO J. 1995 Jul 3;14(13):3116–3126. [PMC free article] [PubMed]
  • Pandey A, Lindberg RA, Dixit VM. Cell signalling. Receptor orphans find a family. Curr Biol. 1995 Sep 1;5(9):986–989. [PubMed]
  • Pandey A, Shao H, Marks RM, Polverini PJ, Dixit VM. Role of B61, the ligand for the Eck receptor tyrosine kinase, in TNF-alpha-induced angiogenesis. Science. 1995 Apr 28;268(5210):567–569. [PubMed]
  • Cheng HJ, Nakamoto M, Bergemann AD, Flanagan JG. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell. 1995 Aug 11;82(3):371–381. [PubMed]
  • Rager G. Morphogenesis and physiogenesis of the retino-tectal connection in the chicken. II. The retino-tectal synapses. Proc R Soc Lond B Biol Sci. 1976 Feb 17;192(1108):353–370. [PubMed]
  • Raper JA, Kapfhammer JP. The enrichment of a neuronal growth cone collapsing activity from embryonic chick brain. Neuron. 1990 Jan;4(1):21–29. [PubMed]
  • Cox EC, Müller B, Bonhoeffer F. Axonal guidance in the chick visual system: posterior tectal membranes induce collapse of growth cones from the temporal retina. Neuron. 1990 Jan;4(1):31–37. [PubMed]
  • Roskies A, Friedman GC, O'Leary DD. Mechanisms and molecules controlling the development of retinal maps. Perspect Dev Neurobiol. 1995;3(1):63–75. [PubMed]
  • Davis S, Gale NW, Aldrich TH, Maisonpierre PC, Lhotak V, Pawson T, Goldfarb M, Yancopoulos GD. Ligands for EPH-related receptor tyrosine kinases that require membrane attachment or clustering for activity. Science. 1994 Nov 4;266(5186):816–819. [PubMed]
  • Sajjadi FG, Pasquale EB. Five novel avian Eph-related tyrosine kinases are differentially expressed. Oncogene. 1993 Jul;8(7):1807–1813. [PubMed]
  • Drescher U, Kremoser C, Handwerker C, Löschinger J, Noda M, Bonhoeffer F. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell. 1995 Aug 11;82(3):359–370. [PubMed]
  • Savitt JM, Trisler D, Hilt DC. Molecular cloning of TOPAP: a topographically graded protein in the developing chick visual system. Neuron. 1995 Feb;14(2):253–261. [PubMed]
  • Flanagan JG, Leder P. The kit ligand: a cell surface molecule altered in steel mutant fibroblasts. Cell. 1990 Oct 5;63(1):185–194. [PubMed]
  • Shao H, Lou L, Pandey A, Verderame MF, Siever DA, Dixit VM. cDNA cloning and characterization of a Cek7 receptor protein-tyrosine kinase ligand that is identical to the ligand (ELF-1) for the Mek-4 and Sek receptor protein-tyrosine kinases. J Biol Chem. 1995 Feb 24;270(8):3467–3470. [PubMed]
  • Ganju P, Shigemoto K, Brennan J, Entwistle A, Reith AD. The Eck receptor tyrosine kinase is implicated in pattern formation during gastrulation, hindbrain segmentation and limb development. Oncogene. 1994 Jun;9(6):1613–1624. [PubMed]
  • Siever DA, Verderame MF. Identification of a complete Cek7 receptor protein tyrosine kinase coding sequence and cDNAs of alternatively spliced transcripts. Gene. 1994 Oct 21;148(2):219–226. [PubMed]
  • Goodman CS. Mechanisms and molecules that control growth cone guidance. Annu Rev Neurosci. 1996;19:341–377. [PubMed]
  • Tessier-Lavigne M. Eph receptor tyrosine kinases, axon repulsion, and the development of topographic maps. Cell. 1995 Aug 11;82(3):345–348. [PubMed]
  • Holash JA, Pasquale EB. Polarized expression of the receptor protein tyrosine kinase Cek5 in the developing avian visual system. Dev Biol. 1995 Dec;172(2):683–693. [PubMed]
  • Holt CE, Harris WA. Position, guidance, and mapping in the developing visual system. J Neurobiol. 1993 Oct;24(10):1400–1422. [PubMed]
  • Walter J, Kern-Veits B, Huf J, Stolze B, Bonhoeffer F. Recognition of position-specific properties of tectal cell membranes by retinal axons in vitro. Development. 1987 Dec;101(4):685–696. [PubMed]
  • Whitelaw VA, Cowan JD. Specificity and plasticity of retinotectal connections: a computational model. J Neurosci. 1981 Dec;1(12):1369–1387. [PubMed]
  • Kozlosky CJ, Maraskovsky E, McGrew JT, VandenBos T, Teepe M, Lyman SD, Srinivasan S, Fletcher FA, Gayle RB, 3rd, Cerretti DP, et al. Ligands for the receptor tyrosine kinases hek and elk: isolation of cDNAs encoding a family of proteins. Oncogene. 1995 Jan 19;10(2):299–306. [PubMed]
  • Wilkinson DG. RNA detection using non-radioactive in situ hybridization. Curr Opin Biotechnol. 1995 Feb;6(1):20–23. [PubMed]
  • Lindberg RA, Hunter T. cDNA cloning and characterization of eck, an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases. Mol Cell Biol. 1990 Dec;10(12):6316–6324. [PMC free article] [PubMed]
  • Willshaw DJ, von der Malsburg C. How patterned neural connections can be set up by self-organization. Proc R Soc Lond B Biol Sci. 1976 Nov 12;194(1117):431–445. [PubMed]
  • Lumsden A. The cellular basis of segmentation in the developing hindbrain. Trends Neurosci. 1990 Aug;13(8):329–335. [PubMed]
  • Maisonpierre PC, Barrezueta NX, Yancopoulos GD. Ehk-1 and Ehk-2: two novel members of the Eph receptor-like tyrosine kinase family with distinctive structures and neuronal expression. Oncogene. 1993 Dec;8(12):3277–3288. [PubMed]
  • Xu Q, Alldus G, Holder N, Wilkinson DG. Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain. Development. 1995 Dec;121(12):4005–4016. [PubMed]
  • McLoon SC. A monoclonal antibody that distinguishes between temporal and nasal retinal axons. J Neurosci. 1991 May;11(5):1470–1477. [PubMed]
  • Mey J, Thanos S. Development of the visual system of the chick--a review. J Hirnforsch. 1992;33(6):673–702. [PubMed]
  • Xu Q, Alldus G, Macdonald R, Wilkinson DG, Holder N. Function of the Eph-related kinase rtk1 in patterning of the zebrafish forebrain. Nature. 1996 May 23;381(6580):319–322. [PubMed]

Articles from The EMBO Journal are provided here courtesy of The European Molecular Biology Organization


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...