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microRNA-194 通过 Fgf4 调控内耳感觉斑和前庭下神经节的发育和分化。

MicroRNA-194 Regulates the Development and Differentiation of Sensory Patches and Statoacoustic Ganglion of Inner Ear by Fgf4.

机构信息

Department of Otolaryngology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China (mainland).

Department of Otolaryngology, Tianjin Medical University General Hospital, Tianjin, China (mainland).

出版信息

Med Sci Monit. 2018 Mar 23;24:1712-1723. doi: 10.12659/msm.906277.

Abstract

BACKGROUND MicroRNA 194 is involved in the differentiation of various types of cells, such as adipose derived stem cells, human embryonic stem cells, and bone marrow mesenchymal stem cells. Previously, we found that miR-194 was highly expressed in the inner ear sensory patch and neurons in mice embryos. However, the role of miR-194 in the development of the inner ear and its underlying mechanism have not been elucidated yet. MATERIAL AND METHODS The expression level of miR-194 has been altered by using antisense morpholino oligonucleotides (MO) and synthesized miRNAs in zebrafish. RESULTS We found that miR-194 was vastly expressed in the inner ear and central nervous system (CNS) in zebrafish. Loss of function of miR-194 could strongly affected the development of zebrafish embryos, including delayed embryonic development, edema of the pericardium, small head, axial deviation, delayed development of inner ear, closer location of two otoliths, delayed fusion of the semicircular canals, and abnormal otolith number in some cases. In addition, the behavior of zebrafish was also adversely affected with impaired balance and biased swimming route. Misexpression of miR-194 could strongly affected the development and differentiation of spiral ganglion neuron (SGN) in inner ear through Fgf4 in vitro. Similar results have also been observed that the overexpression and knockdown of miR-194 strongly disturbed the development and differentiation of the sensory patches and Statoacoustic ganglion (SAG) through Fgf4 in zebrafish in vivo. Our results indicated that miR-194 may regulate the development and differentiation of sensory patches and SAG through Fgf4. CONCLUSIONS Our data revealed a vital role of miR-194 in regulating the development and differentiation of the inner ear.

摘要

背景

MicroRNA 194 参与多种类型细胞的分化,如脂肪来源的干细胞、人类胚胎干细胞和骨髓间充质干细胞。此前,我们发现 miR-194 在小鼠胚胎内耳感觉斑和神经元中高度表达。然而,miR-194 在内耳发育中的作用及其潜在机制尚未阐明。

材料与方法

我们使用反义形态发生素寡核苷酸(MO)和合成 miRNA 改变了斑马鱼中 miR-194 的表达水平。

结果

我们发现 miR-194 在斑马鱼内耳和中枢神经系统(CNS)中广泛表达。miR-194 功能丧失强烈影响斑马鱼胚胎的发育,包括胚胎发育延迟、心包水肿、小头、轴向偏斜、内耳发育延迟、两块耳石更靠近、半规管融合延迟以及在某些情况下耳石数量异常。此外,斑马鱼的行为也受到影响,表现为平衡受损和游泳路线偏向。miR-194 的异位表达通过 Fgf4 在体外强烈影响内耳螺旋神经节神经元(SGN)的发育和分化。在体内,通过 Fgf4,miR-194 的过表达和敲低也强烈干扰了感觉斑和前庭耳蜗神经节(SAG)的发育和分化,得到了类似的结果。我们的结果表明,miR-194 可能通过 Fgf4 调节感觉斑和 SAG 的发育和分化。

结论

我们的数据揭示了 miR-194 在调节内耳发育和分化中的重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f6a/5880017/1b1f60ae1be6/medscimonit-24-1712-g001.jpg

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