The combined effects of trkB and trkC mutations on the innervation of the inner ear
The combined effects of trkB and trkC mutations on the innervation of the inner ear
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DOI：
10.1016/s0736-5748(98)00043-4
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发表时间：
1998-10-01
影响因子：
1.8
通讯作者：
Silos-Santiago, I
中科院分区：
文献类型：
--
作者：
Fritzsch, B;Barbacid, M;Silos-Santiago, I
先前的研究已经证明，只有两种神经营养因子及其同源受体是支持内耳神经支配所必需的。然而，神经营养因子受体突变体的各种组合的神经支配模式的详细分析是缺乏的。我们在这里提供这样一个分析的传入和传出纤维的分布到耳朵的神经营养因子受体突变体的各种组合使用亲脂性示踪剂二碘。在前庭系统中，trkC（+/-）杂合性加剧了trkB（-/-）突变效应，并导致前庭神经元几乎完全丧失。在耳蜗神经支配中，各种突变的特征在于耳蜗罗森塔尔管中螺旋神经元的特定拓扑缺失。单独或与trkB（+/-）杂合性组合的ti trkC（-/-）突变导致所有基底匝螺旋神经元的缺失，传入纤维沿沿着内毛细胞从中间匝延伸到基底匝，对外毛细胞几乎没有贡献。这两种类型的基底转螺旋神经元似乎都是通过放射状纤维发育和投射到内毛细胞，更少的是外毛细胞。简单的trkB（-/-）突变显示，在顶端和不太明显的，在基转外毛细胞的纤维减少。基底回螺旋神经元可能是唯一的神经元存在于出生时在耳蜗的trkB（-/-）突变型小鼠与trkC（+/-）杂合性相结合。此外，trkB（-/-）突变结合trkC（+/-）杂合性在不同窝小鼠中具有斑片状和可变的中匝螺旋神经元丢失。传入和传出纤维的神经支配模式的比较显示出惊人的相似性，没有纤维拓扑相应的领域。例如，在trkC（-/-）突变体中，传入纤维到达基底回，沿耳蜗螺旋沿着，而不是通过放射状纤维，传出纤维遵循相同的路径，而不是从神经节内螺旋纤维发出。所提出的数据表明，有一些偏向特定的螺旋神经节类型的区域特定的影响：trkC是必不可少的支持的基底转螺旋神经元，而trkB似乎是更重要的中间和顶转螺旋神经元。(C)1998年ISDN。由爱思唯尔科技有限公司出版。保留所有权利。
Previous research has demonstrated that only the two neurotrophins and their cognate receptors are necessary for the support of the inner ear innervation. However, detailed analyses of patterns of innervation in various combinations of neurotrophin receptor mutants are lacking. We provide here such an analysis of the distribution of afferent and efferent fibers to the ear in various combinations of neurotrophin receptor mutants using the lipophilic tracer DiI. In the vestibular system, trkC(+/-) heterozygosity aggravates the trkB(-/-) mutation effect and causes almost complete loss of vestibular neurons. In the cochlea innervation, various mutations are each characterized by specific topological absence of spiral neurons in Rosenthal's canal of the cochlea. ti trkC(-/-) mutation alone or in combination with trkB(+/-) heterozygosity causes absence of all basal turn spiral neurons and afferent fibers extend from the middle turn to the basal turn along inner hair cells with little or no contribution to outer hair cells. Both types of basal turn spiral neurons appear to develop and project via radial fibers to inner and, more sparingly, outer hair cells. Simple trkB(-/-) mutations show a-reduction of fibers to outer hair cells in the apex and, less obvious, in the basal turn. Basal turn spiral neurons may be the only neurons present at birth in the cochlea of a trkB(-/-) mutant mouse combined with trkC(+/-) heterozygosity. In addition, the trkB(-/-) mutation combined with trkC(+/-) heterozygosity has a patchy and variable loss of middle turn spiral neurons in mice of different litters. Comparisons of patterns of innervation of afferent and efferent fibers show a striking similarity of absence of fibers to topologically corresponding areas. For example, in trkC(-/-) mutants afferents reach the basal turn, spiraling along the cochlea, rather than through radial fibers and efferent fibers follow the same pathway rather than emanating from intraganglionic spiral fibers. The data presented suggest that there are regional specific effects with some bias towards a specific spiral ganglion type: trkC is essential for support of basal turn spiral neurons whereas trkB appears to be more important for middle and apical turn spiral neurons. (C) 1998 ISDN. Published by Elsevier Science Ltd. All rights reserved.