Deletion of EphA4 enhances deafferentation-induced lpsilateral sprouting in auditory brainstem projections
Deletion of EphA4 enhances deafferentation-induced lpsilateral sprouting in auditory brainstem projections
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DOI：
10.1002/cne.21465
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发表时间：
2007-10-10
影响因子：
2.5
通讯作者：
Cramer, Karina S.
中科院分区：
文献类型：
--
作者：
Hsieh, Candace Y.;Hong, Cindy T.;Cramer, Karina S.
同侧和/或对侧目标的轴突选择对于整合双边感觉信息和协调运动至关重要。决定同侧和对侧目标选择的分子过程尚未完全了解。我们检查了发育中的听觉脑干中的这种目标选择。耳蜗腹核 (VCN) 轴突通常仅在对侧投射到梯形体内侧核 (MNTB)。然而，在单侧去除新生儿的耳蜗输入后，我们发现来自未手术的 VCN 的轴突萌芽并投射到双侧 MNTB。我们发现EphA4在发育过程中和同侧萌芽敏感期在小鼠听觉脑干中表达，因此我们假设删除Eph受体EphA4会损害这些听觉通路中的靶标选择。使用亲脂性染料定量评估野生型和 EphA4 缺失小鼠的脑干投射。 EphA4 缺失小鼠中的 VCN-MNTB 投射完全是对侧的，与野生型小鼠一样。然而，在传入阻滞后，与野生型小鼠相比，EphA4 缺失小鼠的完整 VCN 中长成同侧 MNTB 的轴突比例显着增加了三倍。杂合子小鼠的这些预测增加了一倍。这些结果表明 EphA4 选择性地影响听觉脑干回路以响应传入神经阻滞。尽管这种轴突引导分子本身并不是正常发育过程中适当目标选择所必需的，但它是传入神经阻滞诱导的可塑性过程中同侧与对侧目标选择的重要决定因素。
Axonal selection of ipsilateral and/or contralateral targets is essential for integrating bilateral sensory information and for coordinated movement. The molecular processes that determine ipsilateral and contralateral target choice are not fully understood. We examined this target selection in the developing auditory brainstem. Ventral cochlear nucleus (VCN) axons normally project to the medial nucleus of the trapezoid body (MNTB) only on the contralateral side. However, after unilateral removal of cochlear input in neonates, we found that axons from the unoperated VCN sprout and project to MNTB bilaterally. We found that EphA4 is expressed in the mouse auditory brainstem during development and during a sensitive period for ipsilateral sprouting, so we hypothesized that deletion of the Eph receptor EphA4 would impair target selection in these auditory pathways. Lipophilic dyes were used to evaluate quantitatively the brainstem projections in wild-type and EphA4-null mice. VCN-MNTB projections in EphA4-null mice were strictly contralateral, as in wild-type mice. However, after deafferentation, EphA4-null mice had a significant, threefold increase in the proportion of axons from the intact VCN that sprouted into ipsilateral MNTB compared with wild-type mice. Heterozygous mice had a twofold increase in these projections. These results demonstrate that EphA4 influences auditory brainstem circuitry selectively in response to deafferentation. Although this axon guidance molecule is not by itself necessary for appropriate target choice during normal development, it is a strong determinant of ipsilateral vs. contralateral target choice during deafferentation-induced plasticity.