Actomyosin-Driven Tension at Compartmental Boundaries Orients Cell Division Independently of Cell Geometry In Vivo

Elena Scarpa,Cédric Finet,Guy B Blanchard,Bénédicte Sanson

doi:10.1016/j.devcel.2018.10.029

Abstract

SummaryCell shape is known to influence the plane of cell division. In vitro, mechanical constraints can also orient mitoses; however, in vivo it is not clear whether tension can orient the mitotic spindle directly, because tissue-scale forces can change cell shape. During segmentation of the Drosophila embryo, actomyosin is enriched along compartment boundaries forming supracellular cables that keep cells segregated into distinct compartments. Here, we show that these actomyosin cables orient the planar division of boundary cells perpendicular to the boundaries. This bias overrides the influence of cell shape, when cells are mildly elongated. By decreasing actomyosin cable tension with laser ablation or, conversely, ectopically increasing tension with laser wounding, we demonstrate that local tension is necessary and sufficient to orient mitoses in vivo. This involves capture of the spindle pole by the actomyosin cortex. These findings highlight the importance of actomyosin-mediated tension in spindle orientation in vivo.

Highlights

Regulation of the orientation of cell division is important for tissue morphogenesis, and if defective, can lead to disease such as tumorigenesis (McCaffrey and Macara, 2011), kidney malformations (Fischer et al, 2006), or microcephaly (Megraw et al, 2011)
We find that at these stages, boundary cells (BCs; cells with an edge contributing to a boundary) bias their orientation of division differently from non-boundary cells (NBCs) (Figures 1A–1C)
We discovered that 75% of cells at NEBD have their long axis oriented perpendicular to the AP embryonic axis, and this is true of both BCs and NBCs (Figure S1F)

Summary

Introduction

Regulation of the orientation of cell division is important for tissue morphogenesis, and if defective, can lead to disease such as tumorigenesis (McCaffrey and Macara, 2011), kidney malformations (Fischer et al, 2006), or microcephaly (Megraw et al, 2011). The distribution of the tricellular vertices in the fly notum epithelium was found to be a predictor of the orientation of the mitotic spindle and, in moderately elongated cells, a better predictor than interphase cell shape (Bosveld et al, 2016). Recent work on isolated cells cultured on micropatterns has shown that physical forces may control the orientation of the mitotic spindle independently of cell shape (Fink et al, 2011). It has been observed that tissue-level extrinsic forces can orient the mitotic spindle along the direction of stress (Campinho et al, 2013; Fink et al, 2011; Mao et al, 2013; Wyatt et al, 2015). Because tissue-scale forces cause planar cell elongation in epithelia (Butler et al, 2009; Lye et al, 2015; Mao et al, 2013; Wyatt et al, 2015), it has been difficult to disentangle a direct effect of forces from an indirect effect on cell geometry in vivo (Wyatt et al, 2015)

Methods

Results

Discussion

Conclusion