On the turning of Xenopus retinal axons induced by ephrin-A5

被引:47
作者
Weinl, C
Drescher, U
Lang, S
Bonhoeffer, F
Löschinger, J
机构
[1] Kings Coll London, MRC, Ctr Dev Neurobiol, London SE1 1UL, England
[2] Max Planck Inst Dev Biol, D-72076 Tubingen, Germany
来源
DEVELOPMENT | 2003年 / 130卷 / 08期
关键词
axon guidance; retinotectal projection; ephrin-A5; EphA receptor; Xenopus; growth turning assay; growth cone collapse;
D O I
10.1242/dev.00386
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The Eph family of receptor tyrosine kinases and their ligands, the ephrins, play important roles during development of the nervous system. Frequently they exert their functions through a repellent mechanism, so that, for example, an axon expressing an Eph receptor does not invade a territory in which an ephrin is expressed. Eph receptor activation requires membrane-associated ligands. This feature discriminates ephrins from other molecules sculpturing the nervous system such as netrins, slits and class 3 semaphorins, which are secreted molecules. While the ability of secreted molecules to guide axons, i.e. to change their growth direction, is well established in vitro, little is known about this for the membrane-bound ephrins. Here we set out to investigate - using Xenopus laevis retinal axons - the properties of substratum-bound and (artificially) soluble forms of ephrin-A5 (ephrin-A5-Fc) to guide axons. We find - as expected on the basis of chick experiments that, when immobilised in the stripe assay, ephrin-A5 has a repellent effect such that retinal axons avoid ephrin-A5-Fc-containing lanes. Also, retinal axons react with repulsive turning or growth cone collapse when confronted with ephrin-A5-Fc bound to beads. However, when added in soluble form to the medium, ephrin-A5 induces growth cone collapse, comparable to data from chick. The analysis of growth cone behaviour in a gradient of soluble ephrin-A5 in the 'turning assay' revealed a substratum-dependent reaction of Xenopus retinal axons. On fibronectin, we observed a repulsive response, with the turning of growth cones away from higher concentrations of ephrin-A5. On laminin, retinal axons; turned towards higher concentrations, indicating an attractive effect. In both cases the turning response occurred at a high background level of growth cone collapse. In sum, our data indicate that ephrin-As are able to guide axons in immobilised bound form as well as in the form of soluble molecules. To what degree this type of guidance is relevant for the in vivo situation remains to be shown.
引用
收藏
页码:1635 / 1643
页数:9
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