Regulation of otic neurosensory specification by Notch and Wnt signalling: insights from RNA-seq screenings in the embryonic chicken inner ear.
Regulation of otic neurosensory specification by Notch and Wnt signalling: insights from RNA-seq screenings in the embryonic chicken inner ear.
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DOI：
10.3389/fcell.2023.1245330
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发表时间：
2023
影响因子：
5.5
通讯作者：
Daudet N
中科院分区：
文献类型：
--
作者：
Żak M;Støle TP;Plagnol V;Daudet N
Notch和Wnt信号通路在内耳感觉器官的形成中起着关键作用，但在这种情况下，对它们的转录效应物和靶点知之甚少。在这里，我们通过药物治疗或在卵内电穿孔质粒DNA来干扰胚胎鸡耳囊泡中Notch和Wnt的活性，并使用RNA-Seq分析由此产生的基因表达变化。与药物治疗相比，卵内电穿孔改变了较少基因的表达，这可能是转染的变异性和嵌合性的结果。Notch活性的药理学抑制诱导了该通路已知效应物和神经发生相关基因表达的快速变化，与向听觉神经感觉命运的转变一致。Wnt数据集包含许多与神经感觉生物学功能相关的基因，证实了该途径对耳囊肿神经感觉规范的重要性。最后，对选定的转录因子和Wnt信号成分的初步功能获得筛选结果表明，耳神经感觉规范的内源性程序非常强大，并且通常不受单一因子过表达的影响。本研究对早期内耳发育中Notch和Wnt通路的效应物和候选靶点有了新的认识，可为未来禽类胚胎内耳功能基因组学实验提供有益的参考。
The Notch and Wnt signalling pathways play key roles in the formation of inner ear sensory organs, but little is known about their transcriptional effectors and targets in this context. Here, we perturbed Notch and Wnt activities in the embryonic chicken otic vesicle using pharmacological treatment or in ovo electroporation of plasmid DNA, and used RNA-Seq to analyse the resulting changes in gene expression. Compared to pharmacological treatments, in ovo electroporation changed the expression of fewer genes, a likely consequence of the variability and mosaicism of transfection. The pharmacological inhibition of Notch activity induced a rapid change in the expression of known effectors of this pathway and genes associated with neurogenesis, consistent with a switch towards an otic neurosensory fate. The Wnt datasets contained many genes associated with a neurosensory biological function, confirming the importance of this pathway for neurosensory specification in the otocyst. Finally, the results of a preliminary gain-of-function screening of selected transcription factors and Wnt signalling components suggest that the endogenous programs of otic neurosensory specification are very robust, and in general unaffected by the overexpression of a single factor. Altogether this work provides new insights into the effectors and candidate targets of the Notch and Wnt pathways in the early developing inner ear and could serve as a useful reference for future functional genomics experiments in the embryonic avian inner ear.
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影响因子：
2.5
作者：
Sienknecht, Ulrike J.;Fekete, Donna M.
通讯作者：
Fekete, Donna M.
影响因子：
56.9
作者：
Behrens, J;Jerchow, BA;Birchmeier, W
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BMP4对于检测角头运动的前庭设备的形成至关重要。
影响因子：
4.5
作者：
Chang, Weise;Lin, Zhengshi;Kulessa, Holger;Hebert, Jean;Hogan, Brigid L. M.;Wu, Doris K.
通讯作者：
Wu, Doris K.
影响因子：
4.8
作者：
Bafico, A;Gazit, A;Aaronson, SA
通讯作者：
Aaronson, SA