Mitosis, a springboard for epithelial-mesenchymal transition?

Abstract

Mitosis is a key process in development and remains critical to ensure homeostasis in adult tissues. Besides its primary role in generating two new cells, cell division involves deep structural and molecular changes that might have additional effects on cell and tissue fate and shape. Specific quantitative and qualitative regulation of mitosis has been observed in multiple morphogenetic events in different embryo models. For instance, during mouse embryo gastrulation, the portion of epithelium that undergoes epithelial to mesenchymal transition, where a static epithelial cell become mesenchymal and motile, has a higher mitotic index and a distinct localization of mitotic rounding, compared to the rest of the tissue. Here we explore the potential mechanisms through which mitosis may favor tissue reorganization in various models. Notably, we discuss the mechanical impact of cell rounding on the cell and its environment, and the modification of tissue physical parameters through changes in cell-cell and cell-matrix adhesion.

Occurrence of non-apical mitoses at the primitive streak, induced by relaxation of actomyosin and acceleration of the cell cycle, contributes to cell delamination during mouse gastrulation

“…A higher rate of cell division at the streak therefore appears as a suitable mechanism to fuel gastrulation EMT 11,12 . In addition to its quantitative input, mitosis may also play a qualitative role, notably through the mechanical impact of mitotic rounding on epithelial architecture 44 . The apicobasal position of mitosis may be of importance, as one would instinctively postulate that cells dividing closer to the basal pole have an advantage for subsequent delamination, even if they only detach apically at the late steps of cytokinesis.…”

“…During development, being in constant balance around this critical point may allow embryos to combine robustness and adaptability in order to go through morphogenetic events 49 . Both mitosis and EMT trigger changes in tissue visco-elastic properties that can participate in symmetry breaking, suggesting the applicability of rheology concepts to the epiblast of gastrulating mouse embryos 44 .…”

Completion of neural crest cell production and emigration is regulated by retinoic acid-dependent inhibition of BMP signaling

“…This is consistent with the observed local changes in epithelial architecture, cell cycle properties and basal lamina deposition and might be partially accounted for by the continued emigration of NC cells driving a dorsal shift of interneurons. Along this line, cell shape changes associated with continuous mitosis were reported to impact tissue architecture, including epithelial polarity and cellular EMT (Despin-Guitard and Migeotte, 2021).…”