ABSTRACT The highly ordered wiring of retinal ganglion cell (RGC) neurons in the eye to their synaptic targets in the superior colliculus of the midbrain has long served as the dominant

experimental system for the analysis of topographic neural maps1,2,3. Here we describe a quantitative model for the development of one arm of this map—the wiring of the nasal–temporal axis

of the retina to the caudal–rostral axis of the superior colliculus. The model is based on RGC–RGC competition that is governed by comparisons of EphA receptor signalling intensity, which

are made using ratios of, rather than absolute differences in, EphA signalling between RGCs4. Molecular genetic experiments, exploiting a combinatorial series of EphA receptor knock-in and

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PROJECTION AT SINGLE-CELL PRECISION SUPPORTS LOCAL RETINOTOPY IN THE MOUSE SUPERIOR COLLICULUS Article Open access 16 November 2023 HIGH-DENSITY ELECTRODE RECORDINGS REVEAL STRONG AND

SPECIFIC CONNECTIONS BETWEEN RETINAL GANGLION CELLS AND MIDBRAIN NEURONS Article Open access 05 September 2022 SPATIAL DISTRIBUTION AND FUNCTIONAL INTEGRATION OF DISPLACED RETINAL GANGLION

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homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye. _Development_ 129, 797–804 (2002) CAS  PubMed  Google Scholar  Download references ACKNOWLEDGEMENTS We

thank C. F. Stevens for mathematical insights; M. Dottori and S. Pfaff for the _EphA4_ mutants and _Isl2-τlacZ_ mice, respectively; D. O'Leary, T. McLaughlin and R. Hindges for

discussions and advice on DiI injections; T. Jessell, C. Kintner, M. Meister, S. Pfaff and L. Wolpert for comments on the manuscript; and J. Hash for excellent technical assistance. This

work was supported by grants from the NIH (G.L.), the Philippe Foundation (M.R.), and the Bettencourt–Schueller Foundation (M.R.). M.R. was a fellow from Fondation pour la Recherche

Medicale. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California, 92037, USA Michaël Reber, Patrick Burrola & Greg

Lemke Authors * Michaël Reber View author publications You can also search for this author inPubMed Google Scholar * Patrick Burrola View author publications You can also search for this

author inPubMed Google Scholar * Greg Lemke View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Greg Lemke. ETHICS

DECLARATIONS COMPETING INTERESTS The authors declare that they have no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURE 1 AND DISCUSSION This supplement

elaborates on equations describing the EphA and ephrin-A gradients in the mouse, and discusses the assumption of EphA receptor interchangeability. (PDF 148 kb) SUPPLEMENTARY FIGURE 2 AND

DISCUSSION This supplement describes the direct visualization of EphA3+ axons in heterozygous knock-ins using Isl2-tlacZ as an axonal marker, and its use in multiple compound mutant

backgrounds. (PDF 5616 kb) SUPPLEMENTARY FIGURE 3 AND DISCUSSION This supplement describes a speculative model for how ensemble-wide ratiometric ∑EphA comparisons may be translated into

biased competition for BDNF during axonal competition and map formation in the SC. (PDF 1200 kb) SUPPLEMENTARY DISCUSSION This supplement discusses retinal expression of ephrin-As, and the

implications of results described in the text for their hypothesized roles in retinocollicular mapping. (PDF 64 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Reber, M., Burrola, P. & Lemke, G. A relative signalling model for the formation of a topographic neural map. _Nature_ 431, 847–853 (2004).

https://doi.org/10.1038/nature02957 Download citation * Received: 04 June 2004 * Accepted: 09 August 2004 * Issue Date: 14 October 2004 * DOI: https://doi.org/10.1038/nature02957 SHARE THIS

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