A systems-level approach reveals new gene regulatory modules in the developing ear.
A systems-level approach reveals new gene regulatory modules in the developing ear.
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DOI：
10.1242/dev.148494
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发表时间：
2017-04-15
期刊：
影响因子：
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通讯作者：
Streit A
中科院分区：
文献类型：
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作者：
Chen J;Tambalo M;Barembaum M;Ranganathan R;Simões-Costa M;Bronner ME;Streit A
内耳是一个复杂的脊椎动物感觉器官，但它起源于一个简单的上皮，耳基板。对耳命运的规范需要不同的信号和转录输入，顺序和/或平行作用。利用鸡胚，我们发现新的基因在基因调控网络的基础上耳承诺，并揭示基因表达的动态变化。选择的转录因子的功能分析揭示了遗传层次结构的基础上从祖细胞到承诺的前体，整合已知的和新的分子球员的过渡。我们的研究结果不仅以前所未有的细节表征了耳转录组，而且还确定了负责内耳发育和耳谱系与上鳃祖细胞分离的新基因相互作用。通过重现胚胎程序，这里发现的基因和遗传子电路可能有助于将幼稚细胞重新编程为耳部身份，以恢复听力损失。总结：转录组分析和敲除选择转录因子揭示了遗传层次的细胞成为致力于内耳的命运。
The inner ear is a complex vertebrate sense organ, yet it arises from a simple epithelium, the otic placode. Specification towards otic fate requires diverse signals and transcriptional inputs that act sequentially and/or in parallel. Using the chick embryo, we uncover novel genes in the gene regulatory network underlying otic commitment and reveal dynamic changes in gene expression. Functional analysis of selected transcription factors reveals the genetic hierarchy underlying the transition from progenitor to committed precursor, integrating known and novel molecular players. Our results not only characterize the otic transcriptome in unprecedented detail, but also identify new gene interactions responsible for inner ear development and for the segregation of the otic lineage from epibranchial progenitors. By recapitulating the embryonic programme, the genes and genetic sub-circuits discovered here might be useful for reprogramming naïve cells towards otic identity to restore hearing loss. Summary: Transcriptome analysis and knock down of select transcription factors reveals a genetic hierarchy as cells become committed to inner ear fate.