Bifunctional action of ephrin-B1 as a repellent and attractant to control bidirectional branch extension in dorsal-ventral retinotopic mapping

被引:114
作者
McLaughlin, T [1 ]
Hindges, R [1 ]
Yates, PA [1 ]
O'Leary, DM [1 ]
机构
[1] Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA
来源
DEVELOPMENT | 2003年 / 130卷 / 11期
关键词
axon attraction; axon branching; axon guidance; axon repellents; chick visual system; electroporation; optic tectum; eph receptors; gradients; recombinant retrovirus; topographic maps;
D O I
10.1242/dev.00467
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
We report that the EphB receptor ligand, ephrin-B1, may act bifunctionally as both a branch repellent and attractant to control the unique mechanisms in mapping the dorsal-ventral (DV) retinal axis along the lateral-medial (LM) axis of the optic tectum. EphB receptors are expressed in a low to high DV gradient by retinal ganglion cells (RGCs), and ephrin-B1 is expressed in a low to high LM gradient in the tectum. RGC axons lack DV ordering along the LM tectal axis, but directionally extend interstitial branches that establish retinotopically ordered arbors. Recent studies show that ephrin-B1 acts as an attractant in DV mapping and in controlling directional branch extension. Modeling indicates that proper DV mapping requires that this attractant activity cooperates with a repellent activity in a gradient that mimics ephrin-B1. We show that ectopic domains of high, graded ephrin-B1 expression created by retroviral transfection repel interstitial branches of RGC axons and redirect their extension along the LM tectal axis, away from their proper termination zones (TZs). In contrast, the primary RGC axons are unaffected and extend through the ectopic domains of ephrin-B1 and arborize at the topographically correct site. However, when 2407 the location of a TZ is coincident with ectopic domains of ephrin-B1, the domains appear to inhibit arborization and shape the distribution of arbors. Our findings indicate that ephrin-B1 selectively controls, through either attraction or repulsion, the directional extension and arborization of interstitial branches extended by RGC axons arising from the same DV position: branches that arise from axons positioned lateral to the correct TZ are attracted up the gradient of ephrin-B1 and branches that arise from axons positioned medial to the same TZ are repelled down the ephrin-B1 gradient. Alternatively, EphB receptor signaling may act as a Iligand-density sensor' and titrate signaling pathways that promote branch extension toward an optimal ephrin-B1 concentration found at the TZ; branches located either medial or lateral to the TZ would encounter a gradient of increasingly favored attachment in the direction of the TZ.
引用
收藏
页码:2407 / 2418
页数:12
相关论文
共 50 条
[1]  
Bastmeyer M, 1998, J COMP NEUROL, V392, P1, DOI 10.1002/(SICI)1096-9861(19980302)392:1<1::AID-CNE1>3.0.CO
[2]  
2-6
[3]  
Bastmeyer M, 1996, J NEUROSCI, V16, P1450
[4]  
Birgbauer E, 2000, DEVELOPMENT, V127, P1231
[5]   INVITRO EXPERIMENTS ON AXON GUIDANCE DEMONSTRATING AN ANTERIOR-POSTERIOR GRADIENT ON THE TECTUM [J].
BONHOEFFER, F ;
HUF, J .
EMBO JOURNAL, 1982, 1 (04) :427-431
[6]   Graded and lamina-specific distributions of ligands of EphB receptor tyrosine kinases in the developing retinotectal system [J].
Braisted, JE ;
McLaughlin, T ;
Wang, HU ;
Friedman, GC ;
Anderson, DJ ;
OLeary, DDM .
DEVELOPMENTAL BIOLOGY, 1997, 191 (01) :14-28
[7]   Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target [J].
Brittis, PA ;
Lu, Q ;
Flanagan, JG .
CELL, 2002, 110 (02) :223-235
[8]   Topographic mapping from the retina to the midbrain is controlled by relative but not absolute levels of EphA receptor signaling [J].
Brown, A ;
Yates, PA ;
Burrola, P ;
Ortuño, D ;
Vaidya, A ;
Jessell, TM ;
Pfaff, SL ;
O'Leary, DDM ;
Lemke, G .
CELL, 2000, 102 (01) :77-88
[9]   Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation [J].
Campbell, DS ;
Holt, CE .
NEURON, 2001, 32 (06) :1013-1026
[10]   Control of semaphorin signaling [J].
Castellani, V ;
Rougon, G .
CURRENT OPINION IN NEUROBIOLOGY, 2002, 12 (05) :532-541