MRC Centre for Developmental Neurobiology, King's College London, New Hunt's House, Guy's Campus, London SE1 1UL, UK.
Neural Dev. 2010 Nov 2;5:30. doi: 10.1186/1749-8104-5-30.
Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glycosylphosphatidylinositol-anchored molecules, ephrinAs require transmembrane co-receptors to exert this function, for which the two neurotrophin receptors, p75NTR and TrkB, were recently proposed.
We show here that the ligands for these receptors, the brain-derived neurotrophic factor precursor (proBDNF) and its processed form, BDNF, respectively, control the branching of retinal axons antagonistically, which they mediate by inducing the corresponding neurotrophin receptor-ephrinA complexes. Moreover, scavenging proneurotrophins, by adding antibodies specific for the pro-domain of proBNDF or a soluble extracellular domain of p75NTR, abolish repellent ephrinA reverse signalling in the stripe assay.
This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75NTR interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.
视网膜-视顶盖的投射图形成是通过视网膜轴突在其靶区中的特定拓扑导向和分支来实现的。这个过程部分受到视网膜轴突上表达的外显子反向信号的控制。作为糖基磷脂酰肌醇锚定分子，外显子需要跨膜共受体来发挥此功能，最近提出了两种神经营养因子受体，p75NTR 和 TrkB。
我们在这里表明，这些受体的配体，脑源性神经营养因子前体（proBDNF）及其加工形式 BDNF，分别通过诱导相应的神经营养因子受体-外显子 A 复合物，拮抗地控制视网膜轴突的分支。此外，通过添加针对 proBDNF 前结构域或 p75NTR 可溶性细胞外结构域的抗体来清除神经营养前体，可以消除条纹测定中的排斥性外显子反向信号。
这表明视网膜细胞分泌神经营养前体，诱导外显子 A-p75NTR 相互作用，并使排斥性轴突导向成为可能。proBDNF 和 BDNF 的拮抗作用表明，拓扑分支可能受到神经营养前体加工的局部控制。
