The molecular biology of axon guidance

Science

Volumn 274, Issue 5290, 1996, Pages 1123-1133

  Tessier Lavigne, Marc ^a   Goodman, Corey S ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL ADHESION MOLECULE; LIGAND; PROTEIN TYROSINE KINASE; PROTEIN TYROSINE PHOSPHATASE; RECEPTOR;

CAENORHABDITIS ELEGANS; CELL ADHESION; CELL INTERACTION; CHEMOTAXIS; DROSOPHILA; EVOLUTION; EXTRACELLULAR MATRIX; GROWTH CONE; HUMAN; LIGAND BINDING; MOLECULAR BIOLOGY; NERVE FIBER GROWTH; NONHUMAN; PRIORITY JOURNAL; REVIEW; XENOPUS LAEVIS;

ANIMALS; AXONS; CELL ADHESION MOLECULES, NEURONAL; CELL COMMUNICATION; CELL MOVEMENT; EVOLUTION; HUMANS; LIGANDS; NERVE GROWTH FACTORS; NERVE TISSUE PROTEINS; NERVOUS SYSTEM; NEURAL PATHWAYS; RECEPTORS, CELL SURFACE;

CAENORHABDITIS ELEGANS; XENOPUS LAEVIS;

EID: 0029959555     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.274.5290.1123     Document Type: Review

References (234)

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2. As reviewed by C. S. Goodman and C. J. Shatz [Cell 72, 77 (1993)], the formation of precise patterns of neuronal connections during development appears to involve the sequential operation of two broad sets of mechanisms: those that require electrical activity in neurons (activity-dependent) and those that do not (activity-independent). The events of growth cone guidance and target recognition described here rely on molecular mechanisms that are apparently activity-independent and that result in an intial pattern of projections that is largely accurate, with the exception that at the target some axons can make a set of connections with target cells that is more diffuse than is appropriate. This pattern of connections subsequently becomes more refined and highly tuned under the influence of the precise patterns of electrical activity in the neurons, as discussed in the accompanying review by L. C. Katz and C. J. Shatz [Science 274, 1133 (1996)].
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96. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
97. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
98. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
99. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
100. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
101. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
102. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
103. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
104. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
105. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
106. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
107. T. Elkins, K. Zinn, L. McAllister, F. M. Hoffmann, C. S. Goodman, Cell 60, 565 (1990); P. F. Maness, C. G. Shores, M. Ignelzi, Adv. Exp. Med. Biol. 265, 117 (1990); J. L. Bixby and P. Jhabvala, J. Neurosci. 13, 3421 (1993); E. J. Williams, J. Furness, F. S. Walsh, P. Doherty, Neuron 13, 583 (1994); Development 120, 1685 (1994); P. Doherty and F. S. Walsh, Curr. Opin. Neurobiol. 4, 49 (1994); J. L. Bixby, G. B. Grunwald, R. J. Bookman, J. Cell Biol. 127, 1461 (1994); H. E. Beggs, P. Soriano, P. F. Maness, ibid., p. 825; M. Ignelzi Jr., D. R. Miller, P. Soriano, P. F. Maness, Neuron 12, 873 (1994); E. J. Williams, B. Mittel, F. S. Walsh, P. Doherty, Mol. Cell. Neurosci. 6, 69 (1995); L. Garcia-Alonso, M. F. VanBerkum, G. Grenningloh, C. Schuster, C. S. Goodman, Proc. Natl. Acad. Sci. U.S.A. 92, 10501 (1995); S. G. Klinz, M. Schachner, P. F. Maness, J. Neurochem. 65, 84 (1995); S. Kunz, U. Ziegler, B. Kunz, P. Sonderegger, J. Cell Biol. 135, 253 (1996).
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225. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
226. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
227. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
228. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
229. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
230. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
231. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
232. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
233. Recent studies on signal transduction mechanisms in axon guidance include (46) and J. R Atashi et al., Neuron 8, 831 (1992); W. Li, R. K Herman, J. E. Shaw, Genetics 132, 675 (1992); T P. O'Connor and D. Bentley, J. Cell Biol. 123, 935 (1993 ) ; D. Y. Wu and D. J. Goldberg, ibid., p. 653; L. Aigner et al., Cell 83, 269 (1995); H. Y. Chang et al., Nature 376, 686 (1995); Y. Goshima, F. Nakamura, P. Strittmatter, S. M. Strittmatter, ibid., p. 509; S. M. Strittmatter, C. Fankhauser, P. L. Huang, H. Mashimo, M. C. Fishman, Cell 80, 445 (1995); E. Tanaka and J. Sabry, ibid. 83, 171 (1995); M. F. VanBerkum and C. S. Goodman, Neuron 14, 43 (1995); P. A. Garrity et al., Cell 85, 639 (1996).
234. We thank K. Brose, C. Bargmann, and T. Serfini for thoughtful comments on the manuscript; L. Bauer for help with manuscript preparation; and many colleagues both within our laboratories and around the world who have discussed many of the ideas presented here or who have allowed us to refer to their unpublished results. Supported by NIH grants to M.T.-L. and C.S.G. M.T.-L. is an Assistant Investigator and C.S.G. is an Investigator with the Howard Hughes Medical Institute.