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Research articles

Chaigne, A., Smith, M.B., Lopez Cavestany, R., Hannezo, E., Chalut, K.J., and Paluch, E.K. (2021). Three-dimensional geometry controls division symmetry in stem cell colonies. Journal of Cell Science 134, jcs255018.

We use mouse embryonic stem cells (ESCs), which grow in 3D colonies, as a model to investigate the control of daughter cell size after division in 3D. We show that, at the periphery of 3D colonies, ESCs display high spindle mobility and divide asymmetrically. Our data suggest that enhanced spindle movements are due to unequal distribution of the cell–cell junction protein E-cadherin between future daughter cells. Interestingly, when cells progress towards differentiation, division becomes more symmetric, with more elongated shapes in metaphase and enhanced cortical NuMA recruitment in anaphase. Altogether, this study suggests that in 3D contexts, the geometry of the cell and its contacts with neighbors control division orientation and symmetry.

Chaigne, A., Labouesse, C., White, I.J., Agnew, M., Hannezo, E., Chalut, K.J., and Paluch, E.K. (2020). Abscission Couples Cell Division to Embryonic Stem Cell Fate. Developmental Cell.

In naïve mouse embryonic stem cells, sister cells remain connected for a long time with a cytoplasmic tubulin bridge after cell division. These bridges prevent precocious exit from pluripotency. Upon triggering exit from pluripotency, abscission of the bridges is accelerated correlating with downregulation of pluripotency factors after cell division. Precocious bridge severing accelerates exit from naive pluripotency.

Chaigne, A., C. Labouesse, M. Agnew, E. Hannezo, K.J. Chalut, and E.K. Paluch. 2019. Abscission couples cell division to embryonic stem cell fate. bioRxiv. (now published in part at Dev Cell and in part in JCS)

Dimitracopoulos, A., Srivastava, P., Chaigne, A., Win, Z., Shlomovitz, R., Lancaster, O.M., Le Berre, M., Piel, M., Franze, K., Salbreux, G., et al. (2020). Mechanochemical Crosstalk Produces Cell-Intrinsic Patterning of the Cortex to Orient the Mitotic Spindle. Current Biology.

The mitotic spindle and the spindle positioning force generators (LGN/NuMA/Gai in HeLA cells) have a dynamic cross talk that allow the positioning of the spindle according to the interphase cell long axis without the need for external cues during cell division.

Bennabi, I., Crozet, F., Nikalayevich, E., Chaigne, A., Letort, G., Manil-Ségalen, M., Campillo, C., Cadart, C., Othmani, A., Attia, R., et al. (2020). Artificially decreasing cortical tension generates aneuploidy in mouse oocytes. Nature Communications 11.

When mouse oocyte do not regulate their cortex tension properly and display a low cortex tension, the chromosomes do not align properly at metaphase, leading to aneuploidy. This is due to an increase in cytoplasmic Myosin-II activity,

Smith, M. B., Chaigne, A. & Paluch, E. K. (2016). An active contour ImageJ plugin to monitor daughter cell size in 3D during cytokinesis. In Methods in Cell Biology.

Here we describe an active contour based plugin for Fiji and ImageJ that allows a meshwork segmentation of 3D volumes, in particular applicable to mesure cell volume during cell division.

Chaigne, A., Campillo, C., Voituriez, R., Gov, N.S., Sykes, C., Verlhac, M.-H., and Terret, M.-E. (2016). F-actin mechanics control spindle centring in the mouse zygote. Nat. Commun. 7, 10253.

During the first division of the mouse embryo after in vitro fertilization, the spindle needs to assemble and position without centrioles or astral microtubules. Here we show that the motion of the 2 sets of DNA towards the centre of the cell is actin dependent, the merging of the 2 sets of chromosomes depends on microtubules and the maintainance of the spindle at the centre of the cell depends on a high cortex tension.

Chaigne, A., Campillo, C., Gov, N.S., Voituriez, R., Sykes, C., Verlhac, M.H., and Terret, M.E. (2015). A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte. Nat. Commun. 6, 6027.

Here we show via theoretical modeling and experiments that a small intermediate window of cortex tension is required to allow the spindle to position at the periphery of the cell. if the tension is too high, the spindle stays at the centre of the cell. If the tension is too low, the cortex cannot sustain pulling forces and the spindle cannot migrate either, Only with an intermediate tension can the deformation of the cortex amplify an initial umbalance of forces. We demonstrate that nucleating a thick cortex is sufficient to exclude Myosin-II from the cortex and allow this intermediate tension to be achieved.

Chaigne, A., Campillo, C., Gov, N.S.*, Voituriez, R.*, Azoury, J., Umaña-Diaz, C., Almonacid, M., Queguiner, I., Nassoy, P., Sykes, C., Verlhac, M.-H., Terret, M.-E., 2013. A soft cortex is essential for asymmetric spindle positioning in mouse oocytes. Nat. Cell Biol. 15, 958–966.  

In mouse oocytes, the spindle has to migrate to the periphery of the cell to allow an asymmetric division. Here we show that spindle migration depends on the softening of the cortex, which is due to the nucleation of a thick actin cortex. The branched actin nucleator Arp2/3 is responsible for the nucleation of the cortex under the dependence of the MAPKKK Mos, and in turns allows the exclusion of Myosin-II from the cortex and cortex softening.

Rotation of a 3D segmentation of a colony of mouse embryonic stem cells.
Colony of naïve stem embryonic stem cells with bridges connecting sister cells (microtubules (a-Tubulin): black; midbody (CRIK): red).)

3D segmentation of a colony of mouse Embryonic Stem Cells

Mouse ooycte at the end of spindle migration and before asymmetric division (actin: orange)

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