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脑源性神经营养因子-酪氨酸激酶B轴调节侧线原基的迁移并调控机械感受器祖细胞的维持。

BDNF-TrkB axis regulates migration of the lateral line primordium and modulates the maintenance of mechanoreceptor progenitors.

作者信息

Gasanov Eugene V, Rafieva Lola M, Korzh Vladimir P

机构信息

Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia.

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore, Singapore; Department of Biological Sciences, National University of Singapore, Singapore, Singapore.

出版信息

PLoS One. 2015 Mar 9;10(3):e0119711. doi: 10.1371/journal.pone.0119711. eCollection 2015.

Abstract

BDNF and its specialized receptor TrkB are expressed in the developing lateral line system of zebrafish, but their role in this organ is unknown. To tackle this problem in vivo, we used transgenic animals expressing fluorescent markers in different cell types of the lateral line and combined a BDNF gain-of-function approach by BDNF mRNA overexpression and by soaking embryos in a solution of BDNF, with a loss-of-function approach by injecting the antisence ntrk2b-morpholino and treating embryos with the specific Trk inhibitor K252a. Subsequent analysis demonstrated that the BDNF-TrkB axis regulates migration of the lateral line primordium. In particular, BDNF-TrkB influences the expression level of components of chemokine signaling including Cxcr4b, and the generation of progenitors of mechanoreceptors, at the level of expression of Atoh1a-Atp2b1a.

摘要

脑源性神经营养因子(BDNF)及其特异性受体酪氨酸激酶B(TrkB)在斑马鱼发育中的侧线系统中表达,但其在该器官中的作用尚不清楚。为了在体内解决这个问题,我们使用了在侧线不同细胞类型中表达荧光标记的转基因动物,并将通过BDNF mRNA过表达以及将胚胎浸泡在BDNF溶液中来实现BDNF功能获得的方法,与通过注射反义ntrk2b吗啉代寡核苷酸和用特异性Trk抑制剂K252a处理胚胎来实现功能丧失的方法相结合。随后的分析表明,BDNF-TrkB轴调节侧线原基的迁移。特别是,BDNF-TrkB在Atoh1a-Atp2b1a的表达水平上影响趋化因子信号传导成分(包括Cxcr4b)的表达水平以及机械感受器祖细胞的产生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/686c/4353718/0689c4bf9762/pone.0119711.g001.jpg

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