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Mechanical signals mediated single cell specification in zebrafish ovarian follicle

日期: 2019-05-29
题目:Mechanical signals mediated single cell specification in zebrafish ovarian follicle
主讲人:Peng Xia, Ph.D.
Postdoc fellow
Institute of Science and Technology Austria
For a single cell to acquire a different fate from its surrounding cells, it typically involves a mechanism known as lateral inhibition. In this talk I will show that in zebrafish oogenesis, a group of cells within the granulosa cell layer at the oocyte animal pole acquire elevated levels of the transcriptional coactivator TAZ in their nuclei. One of these cells, the future micropyle precursor cell (MPC), accumulates increasingly high levels of nuclear TAZ and grows faster than its surrounding cells, thereby mechanically compressing those cells, which ultimately lose TAZ from their nuclei. Strikingly, relieving neighbor-cell compression by MPC ablation or aspiration restores nuclear TAZ accumulation in neighboring cells, eventually leading to MPC re-specification from these cells. In addition, TAZ activity promotes mTOR activation, Integrin and Keratin18 expression, and extracellular matrix accumulation, which positively feed back to sustain TAZ hyper-activation in the MPC by activating FAK, Src, PI3K and PDK1 signaling within the MPC. Conversely, MPC specification and its associated features are all defective in taz-/- follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical forces controlling TAZ activity.