Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem.
Graded and discontinuous EphA-ephrinB expression patterns in the developing auditory brainstem.
复制标题
DOI：
10.1016/j.heares.2016.02.013
复制
发表时间：
2016-05
期刊：
影响因子：
2.8
通讯作者：
Gabriele ML
中科院分区：
文献类型：
--
作者：
Wallace MM;Harris JA;Brubaker DQ;Klotz CA;Gabriele ML
Eph-ephrin相互作用在多种系统中引导地形图绘制和图案形成。与其他感觉通路相比，它们在中央听觉回路组装中的确切作用仍然知之甚少。听觉中脑，或下丘（IC）是一个有趣的结构，探索指导模式的投影相邻的分区表现出不同的组织特征。IC的中央核（CNIC）和其相邻的外侧皮层（LCIC，第3层）的深层是音调组织的，并接收来自主要下游听觉源的分层输入。虽然对LCIC的更表面方面知之甚少，但其输入是多模态的，缺乏明确的音调序，并且出现不连续，终止于模块化，斑块/矩阵状分布。在这里，我们利用lacZ突变小鼠（肝配蛋白-B2、-B3和EphA 4）中的X-Gal染色方法来揭示听力开始之前的投射成形期间新生IC中EphA-ephrinB的表达模式。我们还报告了出生后早期在耳蜗核、上级橄榄复合体、外侧丘系核和相关中线结构中的蛋白表达。连续肝配蛋白-B2和EphA 4表达梯度沿CNIC和LCIC层3的沿着频率轴存在。相比之下，更浅表的LCIC定位不分级，但限于一系列离散的肝配蛋白-B2和EphA 4阳性第2层模块。虽然在中线大量表达，但听觉脑干的大部分缺乏ephrin-B3，包括CNIC、LCIC第2层模块场、外侧丘系背核（DNLL）以及上级橄榄复合体和耳蜗核的大部分。肝配蛋白-B3 LCIC表达似乎与肝配蛋白-B2和EphA 4的表达互补，其中蛋白质大多集中在假定的模块外区。所描述的tonotopic梯度和看似互补的模块/模块外模式表明Eph-肝配蛋白指导建立并列的连续和离散的神经地图在开发IC之前的经验。
Eph-ephrin interactions guide topographic mapping and pattern formation in a variety of systems. In contrast to other sensory pathways, their precise role in the assembly of central auditory circuits remains poorly understood. The auditory midbrain, or inferior colliculus (IC) is an intriguing structure for exploring guidance of patterned projections as adjacent subdivisions exhibit distinct organizational features. The central nucleus of the IC (CNIC) and deep aspects of its neighboring lateral cortex (LCIC, Layer 3) are tonotopically-organized and receive layered inputs from primarily downstream auditory sources. While less is known about more superficial aspects of the LCIC, its inputs are multimodal, lack a clear tonotopic order, and appear discontinuous, terminating in modular, patch/matrix-like distributions. Here we utilize X-Gal staining approaches in lacZ mutant mice (ephrin-B2, -B3, and EphA4) to reveal EphA-ephrinB expression patterns in the nascent IC during the period of projection shaping that precedes hearing onset. We also report early postnatal protein expression in the cochlear nuclei, the superior olivary complex, the nuclei of the lateral lemniscus, and relevant midline structures. Continuous ephrin-B2 and EphA4 expression gradients exist along frequency axes of the CNIC and LCIC Layer 3. In contrast, more superficial LCIC localization is not graded, but confined to a series of discrete ephrin-B2 and EphA4-positive Layer 2 modules. While heavily expressed in the midline, much of the auditory brainstem is devoid of ephrin-B3, including the CNIC, LCIC Layer 2 modular fields, the dorsal nucleus of the lateral lemniscus (DNLL), as well as much of the superior olivary complex and cochlear nuclei. Ephrin-B3 LCIC expression appears complementary to that of ephrin-B2 and EphA4, with protein most concentrated in presumptive extramodular zones. Described tonotopic gradients and seemingly complementary modular/extramodular patterns suggest Eph-ephrin guidance in establishing juxtaposed continuous and discrete neural maps in the developing IC prior to experience.