Coordinated Eph-ephrin signaling guides migration and axon targeting in the avian auditory system.
Coordinated Eph-ephrin signaling guides migration and axon targeting in the avian auditory system.
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DOI：
10.1186/1749-8104-7-29
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发表时间：
2012-08-21
影响因子：
3.6
通讯作者：
Cramer KS
中科院分区：
文献类型：
--
作者：
Allen-Sharpley MR;Cramer KS
在鸟类声音定位回路中，大细胞核（NM）向两侧投射到板层核（NL），同侧和对侧 NM 轴突分支分别指向背侧和腹侧 NL 树突。我们之前表明，Eph 受体 EphB2 在发育过程中 NL 神经毡和 NM 轴突中表达。在这里，我们测试了 EphB2 是否有助于 NM-NL 电路的形成。我们发现，当前向信号传导受损时，胚胎 NM 前体中 EphB2 的错误表达显着增加了以细胞自主方式从 NM 到对侧 NL 的轴突靶向错误的数量。我们还通过在 NM 轴突接近其 NL 目标的阶段注射可溶性非簇 Fc 融合蛋白来测试抑制不同 Eph 受体亚类的前向信号传导的效果。我们再次发现，当前向信号传导受损时，与对照组相比，轴突靶向错误增加，当同时抑制两种 Eph 受体亚类时，这种效应显着增加。除了轴突靶向错误之外，我们还观察到当 E2 转染增加 EphB2 前向信号传导时，以及当 E6-E8 注射 Eph 受体融合蛋白抑制 Eph-ephrin 前向信号传导时，听觉核的形态异常。这些数据表明 EphB 信号在轴突引导和形态发生中具有独特的功能。结果证明多个 Eph 受体在精确听觉回路的形成中协同作用。
In the avian sound localization circuit, nucleus magnocellularis (NM) projects bilaterally to nucleus laminaris (NL), with ipsilateral and contralateral NM axon branches directed to dorsal and ventral NL dendrites, respectively. We previously showed that the Eph receptor EphB2 is expressed in NL neuropil and NM axons during development. Here we tested whether EphB2 contributes to NM-NL circuit formation. We found that misexpression of EphB2 in embryonic NM precursors significantly increased the number of axon targeting errors from NM to contralateral NL in a cell-autonomous manner when forward signaling was impaired. We also tested the effects of inhibiting forward signaling of different Eph receptor subclasses by injecting soluble unclustered Fc-fusion proteins at stages when NM axons are approaching their NL target. Again we found an increase in axon targeting errors compared to controls when forward signaling was impaired, an effect that was significantly increased when both Eph receptor subclasses were inhibited together. In addition to axon targeting errors, we also observed morphological abnormalities of the auditory nuclei when EphB2 forward signaling was increased by E2 transfection, and when Eph-ephrin forward signaling was inhibited by E6-E8 injection of Eph receptor fusion proteins. These data suggest that EphB signaling has distinct functions in axon guidance and morphogenesis. The results provide evidence that multiple Eph receptors work synergistically in the formation of precise auditory circuitry.
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DOI：
10.1523/jneurosci.6349-10.2011
发表时间：
2011-08-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Catchpole T;Henkemeyer M
通讯作者：
Henkemeyer M
影响因子：
2.5
作者：
Cramer, KS;Karam, SD;Rubel, EW
通讯作者：
Rubel, EW
影响因子：
16.2
作者：
Hindges, R;McLaughlin, T;O'Leary, DDM
通讯作者：
O'Leary, DDM
影响因子：
25
作者：
Himanen, JP;Chumley, MJ;Nikolov, DB
通讯作者：
Nikolov, DB
影响因子：
64.5
作者：
Dalva, MB;Takasu, MA;Greenberg, ME
通讯作者：
Greenberg, ME