Dataset Information

MicroRNA-206 modulates an Rtn4a/Cxcr4a/Thbs3a axis in newly forming somites to maintain and stabilize the somite boundary formation of zebrafish embryos.

ABSTRACT: Although microRNA-206 (miR-206) is known to regulate proliferation and differentiation of muscle fibroblasts, the role of miR-206 in early-stage somite development is still unknown. During somitogenesis of zebrafish embryos, reticulon4a (rtn4a) is specifically repressed by miR-206. The somite boundary was defective, and actin filaments were crossing over the boundary in either miR-206-knockdown or rtn4a-overexpressed embryos. In these treated embryos, C-X-C motif chemokine receptor 4a (cxcr4a) was reduced, while thrombospondin 3a (thbs3a) was increased. The defective boundary was phenocopied in either cxcr4a-knockdown or thbs3a-overexpressed embryos. Repression of thbs3a expression by cxcr4a reduced the occurrence of the boundary defect. We demonstrated that cxcr4a is an upstream regulator of thbs3a and that defective boundary cells could not process epithelialization in the absence of intracellular accumulation of the phosphorylated focal adhesion kinase (p-FAK) in boundary cells. Therefore, in the newly forming somites, miR-206-mediated downregulation of rtn4a increases cxcr4a. This activity largely decreases thbs3a expression in the epithelial cells of the somite boundary, which causes epithelialization of boundary cells through mesenchymal-epithelial transition (MET) and eventually leads to somite boundary formation. Collectively, we suggest that miR-206 mediates a novel pathway, the Rtn4a/Cxcr4a/Thbs3a axis, that allows boundary cells to undergo MET and form somite boundaries in the newly forming somites of zebrafish embryos.

SUBMITTER: Lin CY

PROVIDER: S-EPMC5541343 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

microRNA-206 modulates an Rtn4a/Cxcr4a/Thbs3a axis in newly forming somites to maintain and stabilize the somite boundary formation of zebrafish embryos.

Lin Cheng-Yung CY He Jun-Yu JY Zeng Chih-Wei CW Loo Moo-Rumg MR Chang Wen-Yen WY Zhang Po-Hsiang PH Tsai Huai-Jen HJ

Open biology 20170701 7

Although microRNA-206 (miR-206) is known to regulate proliferation and differentiation of muscle fibroblasts, the role of miR-206 in early-stage somite development is still unknown. During somitogenesis of zebrafish embryos, reticulon4a (rtn4a) is specifically repressed by miR-206. The somite boundary was defective, and actin filaments were crossing over the boundary in either miR-206-knockdown or rtn4a-overexpressed embryos. In these treat ...[more]

PMID: 28701377

Similar Datasets

Project description:Somite boundary formation is crucial for segmentation of vertebrate somites and vertebrae and skeletal muscle morphogenesis. Previously, we developed a Tol2 transposon-mediated gene trap method in zebrafish. In the present study, we aimed to isolate transposon insertions that trap maternally-expressed genes. We found that homozygous female fish carrying a transposon insertion within a maternally-expressed gene misty somites (mys) produced embryos that showed obscure somite boundaries at the early segmentation stage (12-13 hpf). The somite boundaries became clear and distinct after this period and the embryos survived to adulthood. This phenotype was rescued by expression of mys cDNA in the homozygous adults, confirming that it was caused by a decreased mys activity. We analyzed a role of the mys gene by using morpholino oligonucleotides (MOs). The MO-injected embryo exhibited severer phenotypes than the insertional mutant probably because the mys gene was partially active in the insertional mutant. The MO-injected embryo also showed the obscure somite boundary phenotype. Fibronectin and phosphorylated FAK at the intersomitic regions were accumulated at the boundaries at this stage, but, unlike wild type embryos, somitic cells adjacent to the boundaries did not undergo epithelialization, suggesting that Mys is required for epithelialization of the somitic cells. Then in the MO-injected embryos, the boundaries once became clear and distinct, but, in the subsequent stages, disappeared, resulting in abnormal muscle morphogenesis. Accumulation of Fibronectin and phosphorylated FAK observed in the initial stage also disappeared. Thus, Mys is crucial for maintenance of the somite boundaries formed at the initial stage. To analyze the mys defect at the cellular level, we placed cells dissociated from the MO-injected embryo on Fibronectin-coated glasses. By this cell spreading assay, we found that the mys-deficient cells reduced the activity to form lamellipodia on Fibronectin while FAK was activated in these cells. Thus, we demonstrate that a novel gene misty somites is essential for epithelialization of the somitic cells and maintenance of the somite boundary. Furthermore, Mys may play a role in a cellular pathway leading to lamellipodia formation in response to the Fibronectin signaling. We propose that the Tol2 transposon mediated gene trap method is powerful to identify a novel gene involved in vertebrate development.

Dataset Information

MicroRNA-206 modulates an Rtn4a/Cxcr4a/Thbs3a axis in newly forming somites to maintain and stabilize the somite boundary formation of zebrafish embryos.

Publications

<i>microRNA-206</i> modulates an Rtn4a/Cxcr4a/Thbs3a axis in newly forming somites to maintain and stabilize the somite boundary formation of zebrafish embryos.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets