EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping

EphB forward signaling controls directional branch extension and arborization required for dorsal-ventral retinotopic mapping
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DOI:
10.1016/s0896-6273(02)00799-7
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发表时间:
2002-08-01
期刊:
影响因子:
16.2
通讯作者:
O'Leary, DDM
O'Leary, DDM
中科院分区:
医学1区
文献类型:
--
作者:
Hindges, R;McLaughlin, T;O'Leary, DDM

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我们报道,EphB受体指导着沿着上丘(SC)的背腹(D-V)视网膜轴(L-M轴)定位所需的独特轴突行为。EphB以D-V梯度表达,Ephin-B1以L-M梯度表达,Ephin-B3在其中线表达。EphB和Ephin-B在视网膜和SC中以逆梯度表达。发育分析表明,视网膜轴突沿L-M轴方向缺乏D-V有序性,但沿其方向延伸出分支以建立有序的树枝。定向分支延伸在EphB2中被破坏;EphB3缺陷小鼠导致侧向异位乔木。具有激酶非活性EphB2的小鼠也有类似的D-V映射缺陷,表明正向信号占优势,反向信号占优势。我们的数据表明,表达轴突的EphB分支受到ePhin-B1的中间吸引,并为视觉中心的D-V映射提供了分子机制。
We report that EphB receptors direct unique axonal behaviors required for mapping the dorsal-ventral (D-V) retinal axis along the lateral-medial (L-M) axis of the superior colliculus (SC). EphBs are expressed in a D-V gradient, ephrin-B1 in a L-M gradient in SC, and ephrin-B3 at its midline. EphBs and ephrin-Bs are expressed in countergradients in retina and SC. Developmental analyses reveal that retinal axons lack D-V ordering along the L-M axis, but directionally extend branches along it to establish ordered arbors. Directed branch extension is disrupted in EphB2; EphB3-deficient mice resulting in lateral ectopic arbors. Mice with kinase-inactive EphB2 have similar D-V mapping defects indicating that forward signaling dominates over reverse signaling. Our data suggest that branches of EphB expressing axons are attracted medially by ephrin-B1, and provide molecular mechanisms for D-V mapping in visual centers.