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Proteoglycans as cues for axonal guidance in formation of retinotectal or retinocollicular projections

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Abstract

Understanding the formation of neuronal circuits has long been one of the basic problems in developmental neurobiology. Projections from the retina to their higher center, the optic tectum in nonmammalian vertebrates and the superior colliculus in mammals, are most amenable to experimental approaches; thus, much information has been accumulated about the mechanisms of axonal guidance. The retinal axons navigate along the appropriate pathway with the help of a series of guidance cues. Although much of the work has focused on proteinaceous factors, proteoglycans have been identified as playing important roles in retinal axon guidance. Chondroitin sulfate proteoglycans and heparan sulfate proteoglycans are involved in essential decisions of axon steering along the pathway. However, it has not been determined whether diversity of the carbohydrate chains results in differential effects and how their diversity is recognized by growth cones, which represent an important area of future research.

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References

  1. Goodman C.S. (1996) Mechanisms and molecules that control growth cone guidance. Annu. Rev. Neurosci. 19, 341–377.

    Article  PubMed  CAS  Google Scholar 

  2. Tessier-Lavigne M. and Goodman C.S. (1996) The molecular biology of axon guidance. Science 274, 1123–1133.

    Article  PubMed  CAS  Google Scholar 

  3. Song H.J., Ming G.L., and Poo M.M. (1997) cAMP-induced switching in turning direction of nerve growth cones. Nature 388, 275–279.

    Article  PubMed  CAS  Google Scholar 

  4. Dutting D., Handwerker C., and Drescher U. (1999) Topographic targeting and pathfinding errors of retinal axons following overexpression of ephrinA ligands on retinal ganglion cell axons. Dev. Biol. 216, 297–311.

    Article  PubMed  CAS  Google Scholar 

  5. Hornberger M.R., Dutting D., Ciossek T., Yamada T., Handwerker C., Lang S., et al. (1999) Modulation of EphA receptor function by coexpressed ephrinA ligands on retinal ganglion cell axons. Neuron 22, 731–742.

    Article  PubMed  CAS  Google Scholar 

  6. Holt C.E. and Harris W.A. (1993) Position, guidance, and mapping in the developing visual system. J. Neurobiol. 24, 1400–1422.

    Article  PubMed  CAS  Google Scholar 

  7. Davenport R.W. (1997) Functional guidance components and their cellular distribution in retinotectal co-cultures. Cell Tissue Res. 290, 201–208.

    Article  PubMed  CAS  Google Scholar 

  8. Drescher U., Bonhoeffer F., and Muller B.K. (1997) The Eph family in retinal axon guidance. Curr. Opin. Neurobiol. 7, 75–80.

    Article  PubMed  CAS  Google Scholar 

  9. Karlstrom R.O., Trowe T., and Bonhoeffer F. (1997) Genetic analysis of axon guidance and mapping in the zebrafish. Trends Neurosci. 20, 3–8.

    Article  PubMed  CAS  Google Scholar 

  10. Goodhill G.J. and Richards L.J. (1999) Retinotectal maps: molecules, models and misplaced data. Trends Neurosci. 22, 529–534.

    Article  PubMed  CAS  Google Scholar 

  11. Dingwell K.S., Holt C.E., and Harris W.A. (2000) The multiple decisions made by growth cones of RGCs as they navigate from the retina to the tectum in Xenopus embryos. J. Neurobiol. 44, 246–259.

    Article  PubMed  CAS  Google Scholar 

  12. Mey J. and Thanos S. (2000) Development of the visual system of the chick. I. Cell differentiation and histogenesis. Brain Res. Brain Res. Rev. 32, 343–379.

    Article  PubMed  CAS  Google Scholar 

  13. Thanos S. and Mey J. (2001) Development of the visual system of the chick. II. Mechanisms of axonal guidance. Brain Res. Brain Res. Rev. 35, 205–245.

    Article  PubMed  CAS  Google Scholar 

  14. Knoll B. and Drescher U. (2002) Ephrin-As as receptors in topographic projections. Trends Neurosci. 25, 145–149.

    Article  PubMed  CAS  Google Scholar 

  15. Deiner M.S., Kennedy T.E., Fazeli A., Serafini T., Tessier-Lavigne M., and Sretavan D.W. (1997) Netrin-1 and DCC mediate axon guidance locally at the optic disc: loss of function leads to optic nerve hypoplasia. Neuron 19, 575–589.

    Article  PubMed  CAS  Google Scholar 

  16. Cheng H.J., Nakamoto M., Bergemann A.D., and Flanagan J.G. (1995) Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell 82, 371–381.

    Article  PubMed  CAS  Google Scholar 

  17. Drescher U., Kremoser C., Handwerker C., Loschinger J., Noda M., and Bonhoeffer F. (1995) In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82, 359–370.

    Article  PubMed  CAS  Google Scholar 

  18. Ichijo H. (2003) Roles of proteoglycans in neuronal circuit formation of retinotectal projections. Connective Tissue 35, 11–17.

    CAS  Google Scholar 

  19. Snow D.M., Watanabe M., Letourneau P.C., and Silver J. (1991) A chondroitin sulfate proteoglycan may influence the direction of retinal ganglion cell outgrowth. Development 113, 1473–1485.

    PubMed  CAS  Google Scholar 

  20. Brittis P.A., Canning D.R., and Silver J. (1992) Chondroitin sulfate as a regulator of neuronal patterning in the retina. Science 255, 733–736.

    Article  PubMed  CAS  Google Scholar 

  21. Brittis P.A. and Silver J. (1994) Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium. Proc. Natl. Acad. Sci. USA 91, 7539–7542.

    Article  PubMed  CAS  Google Scholar 

  22. Ohta K., Tannahill D., Yoshida K., Johnson A.R., Cook G.M., and Keynes R.J. (1999) Embryonic lens repels retinal ganglion cell axons. Dev. Biol. 211, 124–132.

    Article  PubMed  CAS  Google Scholar 

  23. Mueller B.K., Ledig M.M., and Wahl S. (2000) The receptor tyrosine phosphatase CRYPalpha affects growth cone morphology. J. Neurobiol. 44, 204–218.

    Article  PubMed  CAS  Google Scholar 

  24. Aricescu A.R., McKinnell I.W., Halfter W., and Stoker A.W. (2002) Heparan sulfate proteoglycans are ligands for receptor protein tyrosine phosphatase sigma. Mol. Cell Biol. 22, 1881–1892.

    Article  PubMed  CAS  Google Scholar 

  25. Inatani M., Honjo M., Otori Y., Oohira A., Kido N., Tano Y., et al. (2001) Inhibitory effects of neurocan and phosphacan on neurite outgrowth from retinal ganglion cells in culture. Invest. Ophthalmol. Vis. Sci. 42, 1930–1938.

    PubMed  CAS  Google Scholar 

  26. Inatani M. and Tanihara H. (2002) Proteoglycans in retina. Prog. Retin. Eye Res. 21, 429–447.

    Article  PubMed  CAS  Google Scholar 

  27. Henke-Fahle S., Wild K., Sierra A., and Monnier P.P. (2001) Characterization of a new brain-derived proteoglycan inhibiting retinal ganglion cell axon outgrowth. Mol. Cell Neurosci. 18, 541–556.

    Article  PubMed  CAS  Google Scholar 

  28. Deiner M.S. and Sretavan D.W. (1999) Altered midline axon pathways and ectopic neurons in the developing hypothalamus of netrin-1- and DCC-deficient mice. J. Neurosci. 19, 9900–9912.

    PubMed  CAS  Google Scholar 

  29. Erskine L., Williams S.E., Brose K., Kidd T., Rachel R.A., Goodman C.S., et al. (2000) Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. J. Neurosci. 20, 4975–4982.

    PubMed  CAS  Google Scholar 

  30. Marcus R.C., Matthews G.A., Gale N.W., Yancopoulos G.D., and Mason C.A. (2000) Axon guidance in the mouse optic chiasm: retinal neurite inhibition by ephrin “A”-expressing hypothalamic cells in vitro. Dev. Biol. 221, 132–147.

    Article  PubMed  CAS  Google Scholar 

  31. Nakagawa S., Brennan C., Johnson K.G., Shewan D., Harris W.A., and Holt C.E. (2000) Ephrin-B regulates the ipsilateral routing of retinal axons at the optic chiasm. Neuron 25, 599–610.

    Article  PubMed  CAS  Google Scholar 

  32. Niclou S.P., Jia L., and Raper J.A. (2000) Slit2 is a repellent for retinal ganglion cell axons. J. Neurosci. 20, 4962–4974.

    PubMed  CAS  Google Scholar 

  33. Chung K.Y., Shum D.K., and Chan S.O. (2000) Expression of chondroitin sulfate proteoglycans in the chiasm of mouse embryos. J. Comp. Neurol. 417, 153–163.

    Article  PubMed  CAS  Google Scholar 

  34. Chung K.Y., Taylor J.S., Shum D.K., and Chan S.O. (2000) Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryos. Development 127, 2673–2683.

    PubMed  CAS  Google Scholar 

  35. Plump A.S., Erskine L., Sabatier C., Brose K., Epstein C.J., Goodman C.S., et al. (2002) Slit1 and Slit2 cooperate to prevent premature midline crossing of retinal axons in the mouse visual system. Neuron 33, 219–232.

    Article  PubMed  CAS  Google Scholar 

  36. Chung K.Y., Leung K.M., Lin L., and Chan S.O. (2001) Heparan sulfate proteoglycan expression in the optic chiasm of mouse embryos. J. Comp. Neurol. 436, 236–247.

    Article  PubMed  CAS  Google Scholar 

  37. Wilson S.W., Ross L.S., Parrett T., and Easter S.S. Jr. (1990) The development of a simple scaffold of axon tracts in the brain of the embryonic zebrafish, Brachydanio rerio. Development 108, 121–145.

    PubMed  CAS  Google Scholar 

  38. Taylor J.S. (1991) The early development of the frog retinotectal projection. Development Suppl 2, 95–104.

    PubMed  CAS  Google Scholar 

  39. Easter S.S. Jr., Ross L.S., and Frankfurter A. (1993) Initial tract formation in the mouse brain. J. Neurosci. 13, 285–299.

    PubMed  Google Scholar 

  40. Chedotal A., Pourquie O., and Sotelo C. (1995) Initial tract formation in the brain of the chick embryo: selective expression of the BEN/SC1/DM-GRASP cell adhesion molecule. Eur. J. Neurosci. 7, 198–212.

    Article  PubMed  CAS  Google Scholar 

  41. Mastick G.S. and Easter S.S. Jr. (1996) Initial organization of neurons and tracts in the embryonic mouse fore- and midbrain. Dev. Biol. 173, 79–94.

    Article  PubMed  CAS  Google Scholar 

  42. Anderson R.B. and Key B. (1999) Novel guidance cues during neuronal pathfinding in the early scaffold of axon tracts in the rostral brain. Development 126, 1859–1868.

    PubMed  CAS  Google Scholar 

  43. Karlstrom R.O., Trowe T., Klostermann S., Baier H., Brand M., Crawford A.D., et al. (1996) Zebrafish mutations affecting retinotectal axon pathfinding. Development 123, 427–438.

    PubMed  CAS  Google Scholar 

  44. Silver J., Poston M., and Rutishauser U. (1987) Axon pathway boundaries in the developing brain. I. Cellular and molecular determinants that separate the optic and olfactory projections. J. Neurosci. 7, 2264–2272.

    PubMed  CAS  Google Scholar 

  45. Ichijo H. and Bonhoeffer F. (1998) Differential withdrawal of retinal axons induced by a secreted factor. J. Neurosci. 18, 5008–5018.

    PubMed  CAS  Google Scholar 

  46. Ichijo H. and Kawabata I. (2001) Roles of the telencephalic cells and their chondroitin sulfate proteoglycans in delimiting an anterior border of the retinal pathway. J. Neurosci. 21, 9304–9314.

    PubMed  CAS  Google Scholar 

  47. Walz A., Anderson R.B., Irie A., Chien C.B., and Holt C.E. (2002) Chondroitin sulfate disrupts axon pathfinding in the optic tract and alters growth cone dynamics. J. Neurobiol. 53, 330–342.

    Article  PubMed  CAS  Google Scholar 

  48. Fricke C., Lee J.S., Geiger-Rudolph S., Bonhoeffer F., and Chien C.B. (2001) Astray, a zebrafish roundabout homolog required for retinal axon guidance. Science 292, 507–510.

    PubMed  CAS  Google Scholar 

  49. McFarlane S., Cornel E., Amaya E., and Holt C.E. (1996) Inhibition of FGF receptor activity in retinal ganglion cell axons causes errors in target recognition. Neuron 17, 245–254.

    Article  PubMed  CAS  Google Scholar 

  50. Chien C.B., Rosenthal D.E., Harris W.A., and Holt C.E. (1993) Navigational errors made by growth cones without filopodia in the embryonic Xenopus brain. Neuron 11, 237–251.

    Article  PubMed  CAS  Google Scholar 

  51. McFarlane S., McNeill L., and Holt C.E. (1995) FGF signaling and target recognition in the developing Xenopus visual system. Neuron 15, 1017–1028.

    Article  PubMed  CAS  Google Scholar 

  52. Walz A., McFarlane S., Brickman Y.G., Nurcombe V., Bartlett P.F., and Holt C.E. (1997) Essential role of heparan sulfates in axon navigation and targeting in the developing visual system. Development 124, 2421–2430.

    PubMed  CAS  Google Scholar 

  53. Irie A., Yates E.A., Turnbull J.E., and Holt C.E. (2002) Specific heparan sulfate structures involved in retinal axon targeting. Development 129, 61–70.

    PubMed  CAS  Google Scholar 

  54. Becker C.G. and Becker T. (2002) Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. J. Neurosci. 22, 842–853.

    PubMed  CAS  Google Scholar 

  55. Schulz M., Raju T., Ralston G., and Bennett M.R. (1990) A retinal ganglion cell neurotrophic factor purified from the superior colliculus. J. Neurochem. 55, 832–841.

    Article  PubMed  CAS  Google Scholar 

  56. Huxlin K.R., Sefton A.J., Schulz M., and Bennett M.R. (1993) Effect of proteoglycan purified from rat superior colliculus on the survival of murine retinal ganglion cells. Brain Res. Dev. Brain Res. 74, 207–217.

    Article  PubMed  CAS  Google Scholar 

  57. Huxlin K.R., Carr R., Schulz M., Sefton A.J., and Bennett M.R. (1995) Trophic effect of collicular proteoglycan on neonatal rat retinal ganglion cells in situ. Brian Res. Dev. Brain Res. 84, 77–88.

    Article  CAS  Google Scholar 

  58. Huxlin K.R., Dreher B., Schulz M., Sefton A.J., and Bennett M.R. (1995) Effect of collicular proteoglycan on the survival of adult rat retinal ganglion cells following axotomy. Eur. J. Neurosci. 7, 96–107.

    Article  PubMed  CAS  Google Scholar 

  59. Wu D.Y., Jhaveri S., and Schneider G.E. (1995) Glial environment in the developing superior colliculus of hamsters in relation to the timing of retinal axon ingrowth. J. Comp. Neurol. 358, 206–218.

    Article  PubMed  CAS  Google Scholar 

  60. Hoffman-Kim D., Lander A.D., and Jhaveri S. (1998) Patterns of chondroitin sulfate immunoreactivity in the developing tectum reflect regional differences in glycosaminoglycan biosynthesis. J. Neurosci. 18, 5881–5890.

    PubMed  CAS  Google Scholar 

  61. Maeda N. and Noda M. (1996) 6B4 proteoglycan/phosphacan is a repulsive substratum but promotes morphological differentiation of cortical neurons. Development 122, 647–658.

    PubMed  CAS  Google Scholar 

  62. Sugahara K. and Yamada S. (2000) Structure and function of oversulfated chondroitin sulfate variants: unique sulfation patterns and neuroregulatory activities. Trends in Glycoscience and Glycotechnology 12, 321–349.

    CAS  Google Scholar 

  63. Varki A., Cummings R., Esko J., Freeze H., Hart G., and Marth J. (1999) Essentials of Glycobiology, Cold Spring Harbor Laboratory Press.

  64. Kitagawa H., Tsutsumi K., Tone Y., and Sugahara K. (1997) Developmental regulation of the sulfation profile of chondroitin sulfate chains in the chicken embryo brain. J. Biol. Chem. 272, 31377–31381.

    Article  PubMed  CAS  Google Scholar 

  65. Erlich R.B., Werneck C.C., Mourao P.A., and Linden R. (2003) Major glycosaminoglycan species in the developing retina: synthesis, tissue distribution and effects upon cell death. Exp. Eye Res. 77, 157–165.

    Article  PubMed  CAS  Google Scholar 

  66. Tanaka M., Maeda N., Noda M., and Marunouchi T. (2003) A chondroitin sulfate proteoglycan PTPzeta /RPTPbeta regulates the morphogenesis of Purkinje cell dendrites in the developing cerebellum. J. Neurosci. 23, 2804–2814.

    PubMed  CAS  Google Scholar 

  67. Monnier P.P., Sierra A., Schwab J.M., Henke-Fahle S., and Mueller B.K. (2003) The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondritin sulfate proteoglycans of the CNS glial scar. Mol. Cell Neurosci. 22, 319–330.

    Article  PubMed  CAS  Google Scholar 

  68. Maeda N., He J., Yajima Y., Mikami T., Sugahara K., Yabe T. (2003) Heterogeneity of the chondroitin sulfate portion of phosphacan/6B4 proteoglycan regulates its binding affinity for pleiotrophin/heparin binding growth-associated molecule. J. Biol. Chem. 278, 35805–35811.

    Article  PubMed  CAS  Google Scholar 

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Ichijo, H. Proteoglycans as cues for axonal guidance in formation of retinotectal or retinocollicular projections. Mol Neurobiol 30, 23–33 (2004). https://doi.org/10.1385/MN:30:1:023

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