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In the formation of projections that map one area of the nervous system onto another, guidance of axonal growth cones by directional cues encoded in target tissues is well established by observations on misrouted fibres, though other mechanisms contribute to the precision of connectivity patterns. General physical principles indicate that, if there is directional guidance of normally as well as misrouted axons, leading them toward their appropriate target positions, the inference for a role of graded distributions of molecules is a strong one. As explained in this paper, curving, meandering, branching and shifting connections are fully consistent with a crucial role of directional cues encoded by graded molecular distributions. A model is proposed according to which slight directional cues are strongly enhanced within the axonal growth cone; if the proximal part of the growth cone is activated indicating that the growth cone points in an entirely wrong direction, then a discontinuous directional change such as branching is elicited. Pathways are corrected in this way, and near the appropriate target position the terminal arbour is formed because from there all routes point towards less optimal positions, leading to multiple branching.
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  J. Xu, W. J. Rosoff, J. S. Urbach, and G. J. Goodhill Adaptation is not required to explain the long-term response of axons to molecular gradients Development, October 15, 2005; 132(20): 4545 - 4552. [Abstract] [Full Text] [PDF]
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 H. Honda Competition between Retinal Ganglion Axons for Targets under the Servomechanism Model Explains Abnormal Retinocollicular Projection of Eph Receptor-Overexpressing or Ephrin-Lacking Mice J. Neurosci., November 12, 2003; 23(32): 10368 - 10377. [Abstract] [Full Text] [PDF]
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T. McLaughlin, R. Hindges, P. A. Yates, and D. D. M. O'Leary Bifunctional action of ephrin-B1 as a repellent and attractant to control bidirectional branch extension in dorsal-ventral retinotopic mapping Development, June 1, 2003; 130(11): 2407 - 2418. [Abstract] [Full Text] [PDF]
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 G. J. Goodhill A Theoretical Model of Axon Guidance by the Robo Code Neural Comput., March 1, 2003; 15(3): 549 - 564. [Abstract] [Full Text] [PDF]
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 H Meinhardt Orientation of chemotactic cells and growth cones: models and mechanisms J. Cell Sci., January 9, 1999; 112(17): 2867 - 2874. [Abstract] [PDF]
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H. Ichijo and F. Bonhoeffer Differential Withdrawal of Retinal Axons Induced by a Secreted Factor J. Neurosci., July 1, 1998; 18(13): 5008 - 5018. [Abstract] [Full Text] [PDF]
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G. C. Friedman and D. D. M. O'Leary Retroviral Misexpression of engrailed Genes in the Chick Optic Tectum Perturbs the Topographic Targeting of Retinal Axons J. Neurosci., September 1, 1996; 16(17): 5498 - 5509. [Abstract] [Full Text] [PDF]
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T Trowe, S Klostermann, H Baier, M Granato, A. Crawford, B Grunewald, H Hoffmann, R. Karlstrom, S. Meyer, B Muller, et al. Mutations disrupting the ordering and topographic mapping of axons in the retinotectal projection of the zebrafish, Danio rerio Development, January 12, 1996; 123(1): 439 - 450. [Abstract] [PDF]
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 A. Roskies and D. O'Leary Control of topographic retinal axon branching by inhibitory membrane-bound molecules Science, August 5, 1994; 265(5173): 799 - 803. [Abstract] [PDF]
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M. Vicker The regulation of chemotaxis and chemokinesis in Dictyostelium amoebae by temporal signals and spatial gradients of cyclic AMP J. Cell Sci., January 2, 1994; 107(2): 659 - 667. [Abstract] [PDF]
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H Baier and F Bonhoeffer Axon guidance by gradients of a target-derived component Science, January 24, 1992; 255(5043): 472 - 475. [Abstract] [PDF]
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