EphA4 provides repulsive signals to developing cochlear ganglion neurites mediated through ephrin-B2 and-B3
EphA4 provides repulsive signals to developing cochlear ganglion neurites mediated through ephrin-B2 and-B3
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DOI：
10.1002/cne.10707
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发表时间：
2003-07-14
影响因子：
2.5
通讯作者：
Ryan, AF
中科院分区：
文献类型：
--
作者：
Brors, D;Bodmer, D;Ryan, AF
肝配蛋白和Eph受体组成了两大家族的双向信号分子，已知它们在神经系统的发育中发挥作用。最近，EphA 4在发育中的耳蜗中的表达被示出，在骨螺旋板（OSL）内衬的细胞中具有强表达，传入树突必须通过骨螺旋板（OSL）到达Corti器（OC）。还证明了肝配蛋白-B2和肝配蛋白-B3（两者都已知与EphA 4相互作用）由螺旋神经节（SG）神经元表达。为了研究EphA 4在内耳神经元发育中的功能作用，将新生大鼠SG外植体在EphA 4/IgG-Fc嵌合体的均匀涂覆的表面或附近条纹上培养72小时。在IgG-Fc和EphAl/IgG-Fc嵌合体上或附近培养对照外植体。为了评估肝配蛋白-B2和-B3在EphA 4信号传导中的作用，将SG外植体与或不与抗肝配蛋白-B2和/或-B3阻断抗体一起培养。在EphA 4受体条纹的边界处的SG神经突的生长模式显示排斥，其特征在于转向、停止和/或逆转。在IgG-Fc和EphA 1的情况下，神经突直接生长在条纹上。用抗肝配蛋白-B2或-B3阻断抗体处理显着降低了EphA 4条纹的排斥作用。此外，当两种抗体一起使用时，神经突交叉到EphA 4条纹上，没有排斥的证据。结果表明，EphA 4提供排斥信号SG神经突在发育中的耳蜗，和ephrin-B2和-B3一起介导这种反应。(C)2003 Wiley-Liss，Inc.
The ephrins and Eph receptors make up two large families of bi-directional signaling molecules that are known to play a role in the development of the nervous system. Recently, expression of EphA4 in the developing cochlea was shown, with strong expression in cells lining the osseous spiral lamina (OSL) through which afferent dendrites must pass to reach the organ of Corti (OC). It was also demonstrated that ephrin-B2 and -B3, both of which are known to interact with EphA4, are expressed by spiral ganglion (SG) neurons. To investigate the functional role of EphA4 in the development of inner ear neurons, neonatal rat SG explants were cultured for 72 hours on uniformly coated surfaces or near stripes of EphA4/IgG-Fc-chimera. Control explants were cultured on or near IgG-Fc and EphA1/IgG-Fc-chimera. To assess the roles of ephrin-B2 and -B3 in EphA4 signaling, SG explants were cultured with or without anti-ephrin-B2 and/or -B3 blocking antibodies. Growth patterns of SG neurites at the border of EphA4 receptor stripes showed repulsion, characterized by turning, stopping and/or reversal. In the case of IgG-Fc and EphA1, the neurites grew straight onto the stripes. Treatment with either anti-ephrin-B2 or -B3 blocking antibodies significantly reduced the repulsive effect of an EphA4 stripe. Moreover, when both antibodies were used together, neurites crossed onto EphA4 stripes with no evidence of repulsion. The results suggest that EphA4 provides repulsive signals to SG neurites in the developing cochlea, and that ephrin-B2 and -B3 together mediate this response. (C) 2003 Wiley-Liss, Inc.