title: Chemoaffinity in topographic mapping revisited--is it more about fiber-fiber than fiber-target interactions?
abstract: Axonal projections between two populations of neurons, which preserve neighborhood relationships, are called topographic. They are ubiquitous in the brain. The development of the retinotectal projection, mapping the retinal output onto the roof of the midbrain, has been studied for decades as a model system. The rigid precision of normal retinotopic mapping has prompted the chemoaffinity hypothesis, positing axonal targeting to be based on fixed biochemical affinities between fibers and targets. In addition, however, abundant evidence has been gathered mainly in the 1970s and 80s that the mapping can adjust to variegated targets with stunning flexibility demonstrating the extraordinary robustness of the guidance process. The identification of ephrins and Eph-receptors as the underlying molecular cues has mostly been interpreted as supporting the fiber-target chemoaffinity hypothesis, while the evidence on mapping robustness has largely been neglected. By having a fresh look on the old data, we expound that they indicate, in addition to fiber-target chemoaffinity, the existence of a second autonomous guidance influence, which we call fiber-fiber chemoaffinity. Classical in vitro observations suggest both influences be composed of opposing monofunctional guidance activities. Based on the molecular evidence, we propose that those might be ephrin/Eph forward and reverse signaling, not only in fiber-target but also in fiber-fiber interactions. In fact, computational models based on this assumption can reconcile the seemingly conflicting findings on rigid and flexible topographic mapping. Supporting the suggested parsimonious and powerful mechanism, they contribute to an understanding of the evolutionary success of robust topographic mass wiring of axons.
authors.affiliation: Institute of Zoology, Department of Cell- and Neurobiology, Karlsruhe Institute of Technology (KIT), Haid-und-Neu-Strasse 9, D-76131 Karlsruhe, Germany. Electronic address: franco.weth@kit.edu.
authors.forename: Franco
authors.initials: F
authors.lastname: Weth
authors.affiliation: Institute of Zoology, Department of Cell- and Neurobiology, Karlsruhe Institute of Technology (KIT), Haid-und-Neu-Strasse 9, D-76131 Karlsruhe, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Fiederling
authors.affiliation: Institut Curie, Centre de Recherche, CNRS U934/URM3215, 11-13, Rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Christoph
authors.initials: C
authors.lastname: Gebhardt
authors.affiliation: Institute of Zoology, Department of Cell- and Neurobiology, Karlsruhe Institute of Technology (KIT), Haid-und-Neu-Strasse 9, D-76131 Karlsruhe, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Bastmeyer
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D001931:Brain Mapping / Q000379:methods; D003198:Computer Simulation; D006801:Humans; D008959:Models, Neurological; D036081:Receptors, Eph Family / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D036081:Receptors, Eph Family
keywords: Axon guidance; Ephrin/Eph; Fiber–fiber interaction; Growth cone; Retinotectal; Topographic map