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Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces.

ABSTRACT: Orientation of cell division is a vital aspect of tissue morphogenesis and growth. Asymmetric divisions generate cell fate diversity and epithelial stratification, whereas symmetric divisions contribute to tissue growth, spreading, and elongation. Here, we describe a mechanism for positioning the spindle in symmetric cell divisions of an embryonic epithelium. We show that during the early stages of epiboly, spindles in the epithelium display dynamic behavior within the plane of the epithelium but are kept firmly within this plane to give a symmetric division. This dynamic stability relies on balancing counteracting forces: an apically directed force exerted by F-actin/myosin-2 via active cortical flow and a basally directed force mediated by microtubules and myosin-10. When both forces are disrupted, spindle orientation deviates from the epithelial plane, and epithelial surface is reduced. We propose that this dynamic mechanism maintains symmetric divisions while allowing the quick adjustment of division plane to facilitate even tissue spreading.

SUBMITTER: Woolner S

PROVIDER: S-EPMC3332010 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces.

Woolner Sarah S Papalopulu Nancy N

Developmental cell 20120308 4

Orientation of cell division is a vital aspect of tissue morphogenesis and growth. Asymmetric divisions generate cell fate diversity and epithelial stratification, whereas symmetric divisions contribute to tissue growth, spreading, and elongation. Here, we describe a mechanism for positioning the spindle in symmetric cell divisions of an embryonic epithelium. We show that during the early stages of epiboly, spindles in the epithelium display dynamic behavior within the plane of the epithelium bu ...[more]

PMID: 22406140

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Project description:During asymmetric division of the Caenorhabditis elegans zygote, to properly distribute cell fate determinants, the mitotic spindle is asymmetrically localized by a combination of centering and cortical-pulling microtubule-mediated forces, the dynamics of the latter being regulated by mitotic progression. Here, we show a, to our knowledge, novel and additional regulation of these forces by spindle position itself. For that, we observed the onset of transverse spindle oscillations, which reflects the burst of anaphase pulling forces. After delaying anaphase onset, we found that the position at which the spindle starts to oscillate was unchanged compared to control embryos and uncorrelated to anaphase onset. In mapping the cortical microtubule dynamics, we measured a steep increase in microtubule contact density after the posterior centrosome reached the critical position of 70% of embryo length, strongly suggesting the presence of a positional switch for spindle oscillations. Expanding a previous model based on a force-generator temporal control, we implemented this positional switch and observed that the large increase in microtubule density accounted for the pulling force burst. Thus, we propose that the spindle position influences the cortical availability of microtubules on which the active force generators, controlled by cell cycle progression, can pull. Importantly, we found that this positional control relies on the polarity-dependent LET-99 cortical band, the boundary of which could be probed by microtubules. This dual positional and temporal control well accounted for our observation that the oscillation onset position resists changes in cellular geometry and moderate variations in the active force generator number. Finally, our model suggests that spindle position at mitosis end is more sensitive to the polarity factor LET-99, which restricts the region of active force generators to a posterior-most region, than to microtubule number or force generator number/activity. Overall, we show that robustness in spindle positioning originates in cell mechanics rather than biochemical networks.

Project description:Successful maintenance of cellular lineages critically depends on the fate decision dynamics of stem cells (SCs) upon division. There are three possible strategies with respect to SC fate decision symmetry: (a) asymmetric mode, when each and every SC division produces one SC and one non-SC progeny; (b) symmetric mode, when 50% of all divisions produce two SCs and another 50%-two non-SC progeny; (c) mixed mode, when both the asymmetric and two types of symmetric SC divisions co-exist and are partitioned so that long-term net balance of the lineage output stays constant. Theoretically, either of these strategies can achieve lineage homeostasis. However, it remains unclear which strategy(s) are more advantageous and under what specific circumstances, and what minimal control mechanisms are required to operate them. Here we used stochastic modeling to analyze and quantify the ability of different types of divisions to maintain long-term lineage homeostasis, in the context of different control networks. Using the example of a two-component lineage, consisting of SCs and one type of non-SC progeny, we show that its tight homeostatic control is not necessarily associated with purely asymmetric divisions. Through stochastic analysis and simulations we show that asymmetric divisions can either stabilize or destabilize the lineage system, depending on the underlying control network. We further apply our computational model to biological observations in the context of a two-component lineage of mouse epidermis, where autonomous lineage control has been proposed and notable regional differences, in terms of symmetric division ratio, have been noted-higher in thickened epidermis of the paw skin as compared to ear and tail skin. By using our model we propose a possible explanation for the regional differences in epidermal lineage control strategies. We demonstrate how symmetric divisions can work to stabilize paw epidermis lineage, which experiences high level of micro-injuries and a lack of hair follicles as a back-up source of SCs.

Dataset Information

Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces.

Publications

Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces.

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