Identification of differentially expressed genes in early inner ear development.

Identification of differentially expressed genes in early inner ear development.
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DOI:
10.1016/j.gep.2009.11.002
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发表时间:
2010-01
影响因子:
1.2
通讯作者:
Schoenwolf, Gary C.
Schoenwolf, Gary C.
中科院分区:
生物学4区
文献类型:
--
作者:
Paxton, Christian N.;Bleyl, Steven B.;Chapman, Susan C.;Schoenwolf, Gary C.

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为了了解先天性听力损失的病因,需要全面了解支持正常耳朵发育的分子遗传机制。我们正在识别与耳发育有关的基因,长期目标是研究它们的作用机制,导致内耳诱导和模式形成。使用安捷伦微阵列,我们比较了测试域(由耳聋前胎盘外胚层与相邻的后脑外胚层和下层中内胚层组织组成)和吻部控制域(包括在外植体分析中有能力表达内耳标记的组织,但不是特定的组织)的差异表达。我们鉴定了1,261个在两个结构域之间差异表达的转录本,变化幅度为2倍或更大:463个在测试结构域中上调,798个在测试结构域中下调。我们通过原位杂交验证了在该阵列中鉴定的几个信号分子和转录因子的差异表达。此外,对测试域中经过验证的一组基因的表达模式进行了详细的探索,以确定它们的表达时间与耳科诱导和发育的特定事件之间的关系。综上所述,我们确定了一些新的耳源性胎盘诱导候选基因。
To understand the etiology of congenital hearing loss, a comprehensive understanding of the molecular genetic mechanisms underlying normal ear development is required. We are identifying genes involved in otogenesis, with the longer term goal of studying their mechanisms of action, leading to inner ear induction and patterning. Using Agilent microarrays, we compared the differential expression of a test domain (which consisted of the pre-otic placodal ectoderm with the adjacent hindbrain ectoderm and the underlying mesendodermal tissues) with a rostral control domain (which included tissue that is competent, but not specified, to express inner ear markers in explant assays). We identified 1,261 transcripts differentially expressed between the two domains at a 2-fold or greater change: 463 were upregulated and 798 were downregulated in the test domain. We validated the differential expression of several signaling molecules and transcription factors identified in this array using in situ hybridization. Furthermore, the expression patterns of the validated group of genes from the test domain were explored in detail to determine how the timing of their expression relates to specific events of otic induction and development. In conclusion, we identified a number of novel candidate genes for otic placode induction.
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