Eine quantitative Analyse der Kräfte und der Mechanik verantwortlich für - Interkinetic Nuclear Migration - im sich entwickelnden Zebrafisch Embryo.
Biophysik
Entwicklungsbiologie
Zusammenfassung der Projektergebnisse
The implementation of this grant proposal resulted in a better understanding of neuroepithelia from cells (part2) to tissue (part1). As neuroepithelia are the building blocks of practically all parts of the vertebrate brain, grasping their cell and developmental biology is of utmost importance for developmental neurobiology. In addition, both parts of the project serve as prime examples how the power of quantitative imaging allows for a much deeper appreciation of biological relations across scales than what can be reached by mere phenomenological observation. Thus, we hope that the outcome of these studies will also serve as inspiration for future investigations in different developing systems. Part 1: Overall, this project elaborated on the important question of how organs coordinate growth with scaling of shape during development. The resulting quantitative dataset will constitute a reference point when assessing other questions of growth in diverse developing tissues. Our results further demonstrate that tissue growth needs to be tightly coordinated to cell shape changes in time and space for successful tissue development and that tissue shape control can occur in concert with the neighboring tissue independently of how the cell would behave in its native environment. This lends further weight to the conclusion that precise coordination of cell-intrinsic and tissue-wide parameters is essential to generate the fully functional, differentiated tissue of correct size and shape. Moving this challenge one step further, a next step will be include 3D studies of growth and shape of ex vivo and organoid cultures and compare findings to in vivo growth. Thus, future studies have the potential to improve engineering of tissues in synthetic and organoid systems. Most importantly however, they will help to fully grasp the complex in vivo programs responsible for the development of all of organisms small and big. Part 2: The main finding of our study was that that the cytoskeletal force generating mechanisms for nuclear positioning vary in similar tissues within the same organism depending on cell and tissue geometry. In particular, we found that apical nuclear migration in pseudostratified neuroepithelia of different cell and tissue shape is driven by distinct actomyosindependent force generating mechanisms. More precisely we unveil that an actomyosin contractility-dependent mechanism, downstream of the Rho-ROCK pathway is responsible for nuclear movements in the straight hindbrain tissue. In contrast, in retinal tissue that shows basally constricted morphology nuclei are pushed by a formin-nucleated expanding actin network. These mechanisms are conserved in tissues of similar shape and changes in cell morphology can lead to adaptation of mechanisms to ensure successful apical nuclear migration. As pseudostratified epithelia are the precursors of diverse organs and importantly most parts of the brain, the variability of mechanisms that ensure apical nuclear migration before mitosis most likely play an important role in successful organogenesis. Further studies are now needed that explore how the cytoskeleton moves nuclei in other epithelial architectures. It is for example not known whether mechanisms differ in apically constricted hindbrain regions or in tissues that thicken over development, like the more mature retinal neuroepithelium (see part 1). It would not surprising to find even more and diverse mechanism to move nuclei to apical positions as our findings suggest that, for pseudostratified epithelial cells, this important end justifies the many means.
Projektbezogene Publikationen (Auswahl)
- (2018) A non-cell-autonomous actin redistribution enables isotropic retinal growth. PLoS Biol, 16(8) Art. No. 2006018
Matejcic M., Salbreux, G., Norden, C.
(Siehe online unter https://doi.org/10.1371/journal.pbio.2006018) - (2016) Heterogeneity, cell biology and tissue mechanics of pseudostratified epithelia: How to coordinate cell divisions and growth in tightly packed tissues. Int Rev Cell Mol Biol. 2016;325:89-118
Strzyz P.J., Matejcic M., Norden, C.
(Siehe online unter https://doi.org/10.1016/bs.ircmb.2016.02.004) - Controlling contractile instabilities in the actomyosin cortex. eLife 2017;6:e19595
Nishikawa, M., Naganathan, S.R., Jülicher, F., Grill, S.W.
(Siehe online unter https://doi.org/10.7554/eLife.19595.001) - 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.
(Siehe online unter https://doi.org/10.1016/bs.mcb.2018.03.017) - Morphogenetic degeneracies in the actomyosin cortex. eLife 2018;7:e37677
Naganathan, S.R., Fürthauer, S,. Rodriguez, J., Fievet, B.T., Jülicher, F., Ahringer, J. Cannistraci, C.V., Grill, S.W.
(Siehe online unter https://doi.org/10.7554/eLife.37677.001) - Guiding self-organized pattern formation in cell polarity establishment. Nat Phys. 2019;15(3):293–300
Gross, P., Kumar, K.V., Goehring, N.W., Bois, J.S., Hoege, C., Jülicher, F., Grill, S.W.
(Siehe online unter https://doi.org/10.1038/s41567-018-0358-7) - Tissue shape determines actin-dependent nuclear migration mechanisms in neuroepithelia. Journal of Cell Biology
Yanakieva I., Erzberger, A., Matejcic M., Modes C.D., Norden C.
(Siehe online unter https://doi.org/10.1083/jcb.201901077)
