Molecular complexity of visual mapping: a challenge for regenerating therapy

MEDORI, MARA; SPELZINI, GONZALO; SCICOLONE, GABRIEL

NEURAL REGENERATION RESEARCH

SHENYANG EDITORIAL DEPT NEURAL REGENERATION RES

Lugar: Shenyang; Año: 2019 vol. 15 p. 382 - 389

1673-5374

Investigating the cellular and molecular mechanisms involved in the development of topographically ordered connections in the central nervous system (CNS) constitutes an important issue in neurobiology because these connections are the base of the CNS normal function. The dominant model to study the development of topographic maps is the projection from the retinal ganglion cells (RGCs) to the optic tectum/colliculus. The expression pattern of Eph/ephrin system in opposing gradients both in the retina and the tectum, labels the local addresses on the target and gives specific sensitivities to growth cones according to their topographic origin in the retina.The rigid precision of normal retinotopic mapping has prompted the chemoaffinityhypothesis, positing axonal targeting to be based on fixed biochemical affinities between fibers and targets. However, several lines of evidence have shown that the mapping can adjust to experimentally modified targets with flexibility, demonstrating the robustness of the guidance process. Here we discuss the complex ways the Ephs and ephrins interact allowing to understand how the retinotectal mapping is a precise but also a flexible process. Thus, fiber-target EphAs/ephrin-As forward and reverse signaling, competition between fiber and target EphAs for fibers ephrin-As, fiber-fiber EphAs/ephrin-As forward and reverse signaling, as a consequence of trans and cis interactions have been described. Besides, different ways of cis interactions ?in parallel with masking properties or in anti-parallel orientation on growth cone surface or insideendosomes inducing signaling have been shown too. All these interactions represent a part of the complex molecular network which regulates axon guidance and retinotectal mapping.The restoration of neural maps is a major aim of visual system repair. The complex molecular interactions of the EphA/ephrin-As system add several variables to take into account to obtain remapping and functional restitution after optic nerve crush or RGCs degeneration, but these complex interactions are also the ones which make the retinotectal/collicular mapping more flexible, opening more possibilities to restitute the map. Understanding these molecular mechanisms would allow us to make a rational manipulation of different factors that could constitute the base of a therapeutic approach to obtain regeneration in the adult CNS. This goal would be the most striking consequence of the old and new studies that are increasing our knowledge about the development of topographically ordered connections in the CNS.