Activation of Six1 Expression in Vertebrate Sensory Neurons.
Activation of Six1 Expression in Vertebrate Sensory Neurons.
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DOI：
10.1371/journal.pone.0136666
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kawakami K
中科院分区：
文献类型：
--
作者：
Sato S;Yajima H;Furuta Y;Ikeda K;Kawakami K
SIX 1同源结构域蛋白是感觉器官发育的重要调控因子之一。Six 1基因缺陷小鼠缺乏嗅上皮、犁鼻器、耳蜗、前庭和前庭听神经节，并且在颅神经节的远端部分也显示出较差的神经分化。Six 1和Six 4的同时缺失会导致其他异常，如小三叉神经节和背根神经节（DRG）异常。本研究的目的是了解控制Six 1在感觉器官中表达的分子机制，特别是在三叉神经节和DRG中。为此，我们专注于感觉神经节特异性Six 1增强子（Six 1 -8）之间的鸡和小鼠保守。使用两种动物的体内报告基因测定鉴定了一个重要的核心区域，其包含几种转录因子的结合共有序列，包括核激素受体、TCF/LEF、SMAD、POU同源结构域和碱性螺旋环螺旋蛋白。这些结果提供了关于上游因素和信号的信息，这些因素和信号可能与感觉神经元中的Six 1调节有关。我们还报告了建立一个新的转基因小鼠系（mSix 1 -8-NLSCre），表达Cre重组酶的控制下的小鼠Six 1 -8。Cre介导的重组在Six 1阳性颅感觉神经节和DRG的ISL 1/2阳性感觉神经元中特异性检测到。mSix 1 -8-NLSCre系的独特特征是在SOX 10阳性神经胶质细胞和中枢神经系统中不存在Cre介导的重组，并且能够在源自嗅基板/上皮的神经元亚组中诱导重组。这种小鼠模型可能用于推进感觉发育的研究。
SIX1 homeodomain protein is one of the essential key regulators of sensory organ development. Six1-deficient mice lack the olfactory epithelium, vomeronasal organs, cochlea, vestibule and vestibuloacoustic ganglion, and also show poor neural differentiation in the distal part of the cranial ganglia. Simultaneous loss of both Six1 and Six4 leads to additional abnormalities such as small trigeminal ganglion and abnormal dorsal root ganglia (DRG). The aim of this study was to understand the molecular mechanism that controls Six1 expression in sensory organs, particularly in the trigeminal ganglion and DRG. To this end, we focused on the sensory ganglia-specific Six1 enhancer (Six1-8) conserved between chick and mouse. In vivo reporter assays using both animals identified an important core region comprising binding consensus sequences for several transcription factors including nuclear hormone receptors, TCF/LEF, SMAD, POU homeodomain and basic-helix-loop-helix proteins. The results provided information on upstream factors and signals potentially relevant to Six1 regulation in sensory neurons. We also report the establishment of a new transgenic mouse line (mSix1-8-NLSCre) that expresses Cre recombinase under the control of mouse Six1-8. Cre-mediated recombination was detected specifically in ISL1/2-positive sensory neurons of Six1-positive cranial sensory ganglia and DRG. The unique features of the mSix1-8-NLSCre line are the absence of Cre-mediated recombination in SOX10-positive glial cells and central nervous system and ability to induce recombination in a subset of neurons derived from the olfactory placode/epithelium. This mouse model can be potentially used to advance research on sensory development.