Spatiotemporally controlled Myosin relocalization and internal pressure cause biased cortical extension to generate sibling cell size asymmetry
Preprint posted on May 01, 2018 https://www.biorxiv.org/content/early/2018/05/01/311852
Context and Background:
Cells of a developing organism can undergo either symmetric or asymmetric cell division. Upon symmetric cell division, the dividing cell generates two daughters of identical fate and size. Asymmetric cell division is a peculiar trait of stem cells and it serves both, self-renewal as well as lineage commitment and differentiation. In the context of cell division, asymmetry is generally meant as asymmetric inheritance of cell fate determinants or as a difference in the type and strength of signal(s) received from the niche. Furthermore, this form of division is often accompanied by asymmetry in cell size.
Drosophila Neuroblasts (NBs) represent a well-established system to study asymmetric stem cell division. These are large cells that repetitively divide to generate another self-renewing neuroblast and a smaller progenitor known as Ganglion Mother Cell (GMC). Neuroblasts generate cell-fate asymmetry by the establishment of a robust polarity axis. The generation of the polarity cues allows the cells to segregate fate determinants to the basal side, ensuring their subsequent inheritance by the future GMC. How cell size asymmetry is generated in the system is still somewhat elusive. Some evidence suggests that an apical-to-basal flow of Myosin-II provides a mean to generate unequally sized daughter cells (Cabernard et al, 2010; Connel et al. 2011; Ou et al. 2010). However it is still unclear by which mechanism Myosin-II promotes physical asymmetry and whether other forces acting on the system contribute to the outcome.
Pham et al. combine atomic force microscopy with the amenability and genetic power of Drosophila and suggest a multi-step model in which coordinated and dynamic changes in cortical tension and hydrostatic pressure direct apical membrane expansion and basal constriction, resulting in sibling size asymmetry (Figure 1). Specifically, they propose that an increase in internal pressure accompanied by a reduction in apical cortical tension drives apical expansion. At the onset of anaphase, once the internal pressure levels drastically reduce to basal level, a contractile ring forms shifted toward the basal side. This basal constriction starts basal membrane expansion and supports apical expansion as well.
Figure1: Proposed working model adopted from Figure 4 of the preprint.
Why I chose this paper:
Are cells smart entities able to receive, interpret and integrate multiple signals and tune their response accordingly? The question of cell intelligence is the big mystery that has been fascinating scientists for decades. How do cells know their relationship with the external environment? How are they able to travel long distances and get to the right place at the right time? Similarly, how do cells know what their right size should be in relation with the outer space and how do they tune their size during growth and division?
I chose the work from Pham and colleagues as they aim to address this latter question by trying to set a molecular base to the establishment of sibling cell asymmetry. This is physiologically relevant especially in the stem cell field, where keeping the right size ratio between the two daughter cells is crucial for cell specification and determination (Ou et al., 2010).
Questions for the Authors:
As the authors mention in the discussion, there is still space for a better characterisation of the process. The model indeed does not explain how internal pressure increases and whether this is under cell-cycle control. Another question would be: what is the membrane reservoir? Is new membrane delivered asymmetrically or asymmetric lipid distribution is achieved lately through the activity of the acto-myosin ring?
This area of research is undoubtedly expanding. In fact, on a smaller scale, one could ask how do cells know the size of their organelles? And by what molecular mechanisms do they control it? In this regard a good example has been recently offered by the Raff lab that published about regulation of centriole size and identified in Plk-4 the “homeostatic clock” which sets the time and rate of centriole growth (Aydogan M. G. et al., 2018).
1. Cabernard, C., Prehoda, K.E., Doe, C.Q., 2010. A spindle-independent cleavage furrow positioning
pathway. Nature 467, 91–94. doi:10.1038/nature09334
2. Connell, M., Cabernard, C., Ricketson, D., Doe, C.Q., Prehoda, K.E., 2011. Asymmetric cortical
extension shifts cleavage furrow position in Drosophila neuroblasts. Mol. Biol. Cell 22, 4220–4226
3. Ou, G., Stuurman, N., D’Ambrosio, M., Vale, R.D., 2010. Polarized myosin produces unequal-size
daughters during asymmetric cell division. Science 330, 677–680. doi:10.1126/science.1196112
4. Mustafa G. Aydogan, ProAlan WainmanSaroj Saurya, Thomas L. Steinacker, Anna Caballe, Zsofia A. Novak, Janina Baumbach, Nadine Muschalik, Jordan W. Raff. A homeostatic clock sets daughter centriole size in flies. Journal of Cell Biology 217 (4), 1233-1248. doi: 10.1083/jcb.201801014
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