Cell fate specification by lateral inhibition typically involves contact signaling through the Delta-Notch signaling pathway. However, whether this is the only signaling mode mediating lateral inhibition remains unclear. Here we 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, 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. Conversely, MPC specification is defective in taz−/− follicles. These findings uncover a novel mode of lateral inhibition in cell fate specification based on mechanical signals controlling TAZ activity.
We thank Roland Dosch, Makoto Furutani-Seiki, Brian Link, Mary Mullins, and Masazumi Tada for providing transgenic and/or mutant zebrafish lines; Alexandra Schauer, Shayan Shami-Pour, and the rest of the Heisenberg lab for technical assistance and feedback on the manuscript; and the Bioimaging, Electron Microscopy, and Zebrafish facilities of IST Austria for continuous support. This work was supported by an ERC advanced grant ( MECSPEC to C.-P.H.).
Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. 2019;176(6):1379-1392.e14. doi:10.1016/j.cell.2019.01.019
Xia, P., Gütl, D. J., Zheden, V., & Heisenberg, C.-P. J. (2019). Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. Elsevier. https://doi.org/10.1016/j.cell.2019.01.019
Xia, Peng, Daniel J Gütl, Vanessa Zheden, and Carl-Philipp J Heisenberg. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” Cell. Elsevier, 2019. https://doi.org/10.1016/j.cell.2019.01.019.
P. Xia, D. J. Gütl, V. Zheden, and C.-P. J. Heisenberg, “Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity,” Cell, vol. 176, no. 6. Elsevier, p. 1379–1392.e14, 2019.
Xia P, Gütl DJ, Zheden V, Heisenberg C-PJ. 2019. Lateral inhibition in cell specification mediated by mechanical signals modulating TAZ activity. Cell. 176(6), 1379–1392.e14.
Xia, Peng, et al. “Lateral Inhibition in Cell Specification Mediated by Mechanical Signals Modulating TAZ Activity.” Cell, vol. 176, no. 6, Elsevier, 2019, p. 1379–1392.e14, doi:10.1016/j.cell.2019.01.019.
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