Competition between retinal ganglion axons for targets under the servomechanism model explains abnormal retinocollicular projection of Eph receptor-overexpressing or ephrin-lacking mice.
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.
Honda
Hisao
H
Hyogo University, Hyogo 675-0195, Japan. hihonda@hyogo-dai.ac.jp
D000818:Animals; D001369:Axons / Q000502:physiology*; D003198:Computer Simulation; D036342:Ephrins / Q000172:deficiency* / Q000235:genetics; D006579:Heterozygote; D006720:Homozygote; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008959:Models, Neurological; D036082:Receptor, EphA1 / Q000096:biosynthesis* / Q000235:genetics; D012160:Retina / Q000166:cytology / Q000502:physiology; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology
D036342:Ephrins; D008024:Ligands; D036082:Receptor, EphA1