Disorganized innervation and neuronal loss in the inner ear of Slitrk6-deficient mice.
Disorganized innervation and neuronal loss in the inner ear of Slitrk6-deficient mice.
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DOI：
10.1371/journal.pone.0007786
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发表时间：
2009-11-11
期刊：
影响因子：
3.7
通讯作者：
Aruga J
中科院分区：
文献类型：
--
作者：
Katayama K;Zine A;Ota M;Matsumoto Y;Inoue T;Fritzsch B;Aruga J
Slitrks是I型跨膜蛋白，其共享与分泌的轴突引导分子Slit中的那些类似的保守的富含亮氨酸的重复结构域。它们还在其羧基末端显示出与Ntrk神经营养因子受体的相似性，共享保守的酪氨酸残基。在哺乳动物的6个Slitrk家族基因中，Slitrk 6具有独特的表达模式，在内耳感觉上皮中强表达。我们产生了Slitrk 6基因敲除小鼠，并研究了它们的听觉和前庭感觉器官的发育。Slitrk 6缺陷小鼠表现出耳蜗神经支配的明显减少。在前庭，后嵴的神经支配经常丢失、减少或有时被误导。这些缺陷伴随着螺旋神经节和前庭神经节中神经元的丢失。Slitrk 6基因敲除小鼠的耳蜗感觉上皮细胞促进螺旋神经节神经元突起生长的能力降低。事实上，Slitrk 6缺陷型内耳显示出Bdnf和Ntf 3表达的轻微但显著的降低，这两者对于感觉神经元的神经支配和存活都是必不可少的。此外，Ntrk受体的表达，包括其磷酸化形式在Slitrk 6敲除耳蜗中降低。这些结果表明，Slitrk 6通过调节来自感觉上皮的营养因子和/或营养因子（包括神经营养因子）的表达来促进内耳感觉神经元的神经支配和存活。
Slitrks are type I transmembrane proteins that share conserved leucine-rich repeat domains similar to those in the secreted axonal guidance molecule Slit. They also show similarities to Ntrk neurotrophin receptors in their carboxy-termini, sharing a conserved tyrosine residue. Among 6 Slitrk family genes in mammals, Slitrk6 has a unique expression pattern, with strong expression in the sensory epithelia of the inner ear. We generated Slitrk6-knockout mice and investigated the development of their auditory and vestibular sensory organs. Slitrk6-deficient mice showed pronounced reduction in the cochlear innervation. In the vestibule, the innervation to the posterior crista was often lost, reduced, or sometimes misguided. These defects were accompanied by the loss of neurons in the spiral and vestibular ganglia. Cochlear sensory epithelia from Slitrk6-knockout mice have reduced ability in promoting neurite outgrowth of spiral ganglion neurons. Indeed the Slitrk6-deficient inner ear showed a mild but significant decrease in the expression of Bdnf and Ntf3, both of which are essential for the innervation and survival of sensory neurons. In addition, the expression of Ntrk receptors, including their phosphorylated forms was decreased in Slitrk6-knockout cochlea. These results suggest that Slitrk6 promotes innervation and survival of inner ear sensory neurons by regulating the expression of trophic and/or tropic factors including neurotrophins from sensory epithelia.
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DOI：
10.1002/neu.10098
发表时间：
2002-11-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Fritzsch, B;Beisel, KW;Reichardt, LF
通讯作者：
Reichardt, LF
影响因子：
2.8
作者：
FRITZSCH, B;NICHOLS, DH
通讯作者：
NICHOLS, DH
DOI：
10.1016/s0736-5748(98)00043-4
发表时间：
1998-10-01
影响因子：
1.8
作者：
Fritzsch, B;Barbacid, M;Silos-Santiago, I
通讯作者：
Silos-Santiago, I
影响因子：
3.5
作者：
Aruga, J;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
2.7
作者：
Inoue, T;Hatayama, M;Mikoshiba, K
通讯作者：
Mikoshiba, K