Investigating the impact of centrosome number on neuroepithelial maturation and proliferative compensation
Cell Biology
Final Report Abstract
We here made initial headway in understanding what happens to cells that overexpress Plk4 and thereby feature amplified centrosomes with respect to cell cycle control. Our initial results show that cell cycle length can be altered upon Plk4 overexpression compared to controls, but these changes depend on the imaging system used. Upon light sheet microscopy cell cycle length increases in Plk4 overexpressing cells with amplified centrosomes. The reason for this could be an increased mitotic timing due to spindle formation problems or overall increased cell cycle length due to Plk4 overexpression per se which might trigger some cell cycle checkpoint at later cell cycle stages. When the same analysis is done with a spinning disk microscope however, cell cycle length in control neuroepithelia increases, most likely due to photodamage, but Plk4 overexpressing cells show similar cell cycle length as when imaged on the light sheet. We show that the biggest difference on cell cycle timing between controls and Plk4 overexpressing cells occurs in S- phase, the cell cycle phase when usually DNA damage (that can be induced by phototoxicity as shown here and elsewhere) is repaired. These results argue that Plk4 overexpressing cells somehow shut down the S-phase checkpoint. Next it needs to be tested whether this phenomenon is specific to DNA damage induced by phototoxicity or applies to DNA damage overall. It will also be important to check whether this reduction of checkpoint activity results from Plk4 overexpression per se or can be linked to amplified centrosomes and how conserved phenomena are outside the zebrafish neuroepithelial system.
Publications
- (2018) Choosing the right microscope to image mitosis in zebrafish embryos: A practical guide Methods Cell Biol. 2018;145:107-127
Yanakieva, I., Matejcic M., Norden C.
(See online at https://doi.org/10.1016/bs.mcb.2018.03.017) - (2019) Tissue shape determines actin-dependent nuclear migration mechanisms in neuroepithelia J Cell Biol.
Yanakieva I., Erzberger, A., Matejcic M., Modes C.D., Norden C.
(See online at https://doi.org/10.1083/jcb.201901077)
