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The Journal of Neuroscience, November 12, 2003, 23(32):10368-10377

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Development/Plasticity/Repair
Competition between Retinal Ganglion Axons for Targets under the Servomechanism Model Explains Abnormal Retinocollicular Projection of Eph Receptor-Overexpressing or Ephrin-Lacking Mice

Hisao Honda

Hyogo University, Hyogo 675-0195, Japan

Topographic mapping of retinal ganglion axons to the midbrain is computed by the servomechanism model, which is based on the experimental result of cell attachment. Cells expressing a certain level of Eph proteins (receptors for ephrin ligands) optimally attach to a surface that expresses a specific level of ephrin ligand density. The retina has an increasing nasal-to-temporal gradient of Eph receptor density, and the optic tectum/superior colliculus has an increasing rostral-to-caudal gradient of membrane-bound ephrin ligand. An axon from the retina has an identification tag of a certain level of Eph receptor density depending on its retinal position and adheres to the site on the tectum/superior colliculus expressing ephrin ligands at a critical ligand density level. Quantitatively, a retinal axon has a receptor density (R) that is determined by its retinal position, and the axon terminal is induced to adhere to the tectal site of ligand density (L = S/R), where S is a constant. Consequently, the servomechanism model defines positions of axon terminals on the midbrain. Abnormal topographic maps are reported in a knock-in experiment with elevated density of Eph receptors and a knock-out experiment lacking ephrin ligands using gene-targeting technology. By adding competition between axon terminals for target sites to the servomechanism model, the abnormal maps became easy to understand. Furthermore, the servomechanism-competition model allowed conjecture of the gradient shapes of receptor and ligand densities and estimation of the capacity of the midbrain surface to accept retinal axon terminals.

Key words: competition; computer simulation; knock-in; knock-out; neural axon; projection; retina; servomechanism; superior colliculus; tectum; topographic map

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Received July 26, 2003; revised September 16, 2003; accepted September 18, 2003.

This article has been cited by other articles:

				D. Willshaw Analysis of mouse EphA knockins and knockouts suggests that retinal axons programme target cells to form ordered retinotopic maps Development, July 15, 2006; 133(14): 2705 - 2717. [Abstract] [Full Text] [PDF]

				A. C. von Philipsborn, S. Lang, J. Loeschinger, A. Bernard, C. David, D. Lehnert, F. Bonhoeffer, and M. Bastmeyer Growth cone navigation in substrate-bound ephrin gradients Development, July 1, 2006; 133(13): 2487 - 2495. [Abstract] [Full Text] [PDF]

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