Development of the visual system of the chick II. Mechanisms of axonal guidance

The quest to understand axonal guidance mechanisms requires exact and multi disciplinary analyses of axon navigation. This review is the second part of an attempt to synthesise experimental data with theoretical models of the development of the topographic connection of the chick retina with the tect um. The first part included classic ideas from developmental biology and re cent achievements on the molecular level in understanding cytodifferentiati on and histogenesis [J. Mey, S. Thanes, Development of the visual system of the chick. (I) Cell differentiation and histogenesis, Brain Res. Rev. 32 ( 2000) 343-379]. The present part deals with the question of how millions of fibres exit from the eye, traverse over several millimetres and spread ove r the optic tectum to assemble a topographic map, whose precision accounts for the sensory performance of the visual system. The following topics gain ed special attention in this review. (i) A remarkable conceptual continuity between classic embryology and recent molecular biology has revealed that positional cellular specification precedes and determines the formation of the retinotectal map, (ii) Graded expression of asymmetric genes, transcrip tional factors and receptors for signal transduction during early developme nt seem to play a crucial role in determining the spatial identity of neuro ns within surface areas of retina and optic tectum. (iii) The chemoaffinity hypothesis constitutes the conceptual framework for development of the ret inotopic organisation of the primary visual pathway. Studies of repulsive f actors in vitro developed the original hypothesis from a theoretical postul ate of chemoattraction to an empirically supported concept based on chemore pulsion. (iv) The independent but synchronous development of retina and opt ic tectum in topo-chronologically corresponding patterns ensures that ingro wing retinal axons encounter receptive target tissue at appropriate locatio ns, and at the time when connections are due to be formed. (v) The growth c ones of the retino-fugal axons seem to be guided both by local cues on glia l endfeet and within the extracellular matrix. On the molecular level, the ephrins and their receptors have emerged as the most likely candidates for the material substrate of a topographic projection along the anterior-poste rior axis of the optic tectum. Yet, since a number of alternative molecules have been proposed for the same function, it remains the challenge for the near future to define the proportional contribution of each one of the ind ividual mechanisms proposed by matching theoretical predictions with the ex perimental evidence. (C) 2001 Elsevier Science B.V. All rights reserved.