Mechanical and Molecular Regulation of Periodic Cortical Waves of Contraction ; Régulation mécanique et moléculaire des vagues corticales périodiques de la contraction
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Medientyp:
E-Book
Titel:
Mechanical and Molecular Regulation of Periodic Cortical Waves of Contraction ; Régulation mécanique et moléculaire des vagues corticales périodiques de la contraction
Erschienen:
[Erscheinungsort nicht ermittelbar]: HAL CCSD, 2021
Sprache:
Englisch
Entstehung:
Hochschulschrift:
Dissertation, HAL CCSD, 2021
Anmerkungen:
Beschreibung:
During pre-implantation development, the mammalian embryo forms the blastocyst, which is the structure embedding the embryo into the uterus. The shaping of the blastocyst relies in large part on contractile forces generated by the actomyosin cortex. In the mouse, on timescales of seconds, we observe pulses of actomyosin contractions traveling periodically around the cell perimeter. We call this phenomenon periodic cortical waves of contraction (PeCoWaCo), a fascinating and poorly understood manifestation of contractility. In this study, we take advantage of the slow development of the mouse embryo to study thousands of contraction pulses and of the robustness of the mouse embryo to size manipulation to explore the biophysical properties of PeCoWaCo during the cleavage stages preceding early mammalian morphogenesis. We find that, during cleavage stages, periodic movements appear occasionally at the zygote and the 2-cell stage and become systematic after the 2nd round of cleavage divisions. Interestingly, the period of oscillations progressively decreases from 200 s at the zygote stage to 80 s at the 8-cell stage. Since cells becomes successively smaller with successive cleavage divisions, cell size could be an important determinant in the initiation and regulation of PeCoWaCo. We manipulate cell size on a broad range of cell radii (10-40 µm) using fragmentation and fusion of cells and find that the initiation, persistence or properties of PeCoWaCo do not depend on cell size. Following the period of PeCoWaCo, we discover that blastomeres gradually decrease their surface tensions until the 8-cell stage and that artificially softening cells enhances PeCoWaCo prematurely. Therefore, during cleavage stages, cortical softening awakens zygotic contractility before preimplantation morphogenesis. In addition, by manipulating actomyosin contractility using mutants and drugs, we showed that the period of PeCoWaCo can be tuned by F-actin polymerization rate and myosin motor activity. Altogether our results on biophysical and ...