A search for factors specifying tonotopy implicates DNER in hair-cell development in the chick's cochlea.
A search for factors specifying tonotopy implicates DNER in hair-cell development in the chick's cochlea.
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DOI：
10.1016/j.ydbio.2011.03.031
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发表时间：
2011-06-15
影响因子：
2.7
通讯作者：
Hudspeth AJ
中科院分区：
文献类型：
--
作者：
Kowalik L;Hudspeth AJ
脊椎动物对声音频率的准确感知依赖于毛细胞的调节，毛细胞沿着听觉器官排列，根据频率进行调节。这种排列被称为异位梯度，是许多细胞和细胞外特征协调的结果。为了寻找协调这些特征和控制异位梯度的机制，我们使用表达微阵列来鉴定鸡（Gallus Gallus）耳蜗高频和低频区域之间差异表达的基因。在结果中广泛代表的三种信号系统中，我们专注于缺口途径，特别是DNER，一种假定的缺口配体，以及PTPζ，一种控制DNER运输的受体磷酸酶。免疫组织化学证实，这两种蛋白在耳蜗尖毛细胞中的表达比在耳蜗基部毛细胞中的表达更强烈。在每个毛细胞的顶端表面，蛋白质显示极化，相互排斥的定位模式。使用morpholinos来降低DNER或PTPζ的表达，以及逆转录病毒载体来过表达DNER，我们观察到毛束形态和方向的干扰。我们的研究结果表明，DNER和PTPζ在毛细胞发育中起作用，并可能在毛细胞toptopy的规范中起作用。
The accurate perception of sound frequency by vertebrates relies upon the tuning of hair cells, which are arranged along auditory organs according to frequency. This arrangement, which is termed a tonotopic gradient, results from the coordination of many cellular and extracellular features. Seeking the mechanisms that orchestrate those features and govern the tonotopic gradient, we used expression microarrays to identify genes differentially expressed between the high- and low-frequency cochlear regions of the chick (Gallus gallus). Of the three signaling systems that were represented extensively in the results, we focused on the notch pathway and particularly on DNER, a putative notch ligand, and PTPζ, a receptor phosphatase that controls DNER trafficking. Immunohistochemistry confirmed that both proteins are expressed more strongly in hair cells at the cochlear apex than in those at the base. At the apical surface of each hair cell, the proteins display polarized, mutually exclusive localization patterns. Using morpholinos to decrease the expression of DNER or PTPζ as well as a retroviral vector to overexpress DNER, we observed disturbances of hair-bundle morphology and orientation. Our results suggest a role for DNER and PTPζ in hair-cell development and possibly in the specification of tonotopy.
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.0608536103
发表时间：
2006-12-05
影响因子：
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Hudspetht, A. J.
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