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

The quest to understand axonal guidance mechanisms requires exact and multidisciplinary 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 tectum. The first part included classic ideas from developmental biology and recent achievements on the molecular level in understanding cytodifferentiation and histogenesis [J. Mey, S. Thanos, 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 over the optic tectum to assemble a topographic map, whose precision accounts for the sensory performance of the visual system. The following topics gained 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, transcriptional factors and receptors for signal transduction during early development seem to play a crucial role in determining the spatial identity of neurons within surface areas of retina and optic tectum. (iii) The chemoaffinity hypothesis constitutes the conceptual framework for development of the retinotopic organisation of the primary visual pathway. Studies of repulsive factors in vitro developed the original hypothesis from a theoretical postulate of chemoattraction to an empirically supported concept based on chemorepulsion. (iv) The independent but synchronous development of retina and optic tectum in topo-chronologically corresponding patterns ensures that ingrowing retinal axons encounter receptive target tissue at appropriate locations, and at the time when connections are due to be formed. (v) The growth cones of the retino-fugal axons seem to be guided both by local cues on glial 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-posterior 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 individual mechanisms proposed by matching theoretical predictions with the experimental evidence.