The force and effect of cell proliferation.

The spatiotemporal control of cell divisions is a key factor in epithelial morphogenesis and patterning. Mao et al (2013) now describe how differential rates of proliferation within the Drosophila wing disc epithelium give rise to anisotropic tissue tension in peripheral/proximal regions of the disc. Such global tissue tension anisotropy in turn determines the orientation of cell divisions by controlling epithelial cell elongation. Oriented cell divisions play important roles in the establishment of the animal body plan by both influencing tissue morphogenesis and generating cellular diversity. Generally, the direction of the cell division plane is determined by the orientation of the mitotic spindle prior to cytokinesis. The observation that the mitotic spindle in most animal cell types aligns with the cell’s longest axis has led to the formulation of the ‘long-axis-rule’, postulating that cell shape anisotropy is the main determinant of spindle orientation (Minc et al, 2011). However, cell shape anisotropy is unlikely to be the only determinant since many cell types round up during mitosis, thereby losing their shape anisotropy and others do not follow the long-axis-rule at all. In such cases, division orientation is determined by the polarizing activity of biochemical signals originating from the environment (reviewed in Morin and Bellaı̈che, 2011). In addition, externally applied forces have also been suggested to control division orientation of single cells in culture independently from their effect on cell shape (Fink et al, 2011). Epithelial growth implies that cells divide parallel to the tissue plane with both daughter cells remaining integrated within the tissue. Although it has been recognized that defects in apico-basal polarity lead to spindle misalignment and disruption of epithelial architecture, the molecular mechanisms underlying this regulation are still unknown. Recent work in the Drosophila wing disc epithelium uncovered that the junctional proteins Scribbled and Discs large 1 (Dlg1) are required for proper spindle alignment parallel to the tissue plane (Nakajima et al, 2013). Similarly, in the Drosophila follicular epithelium, spindle orientation is dependent on the lateral localization of Dlg1, independently of its role in apico-basal polarity (Bergstralh et al, 2013). While such mechanisms ensure that cells divide parallel to the epithelial plane, other mechanisms must still be present to determine the orientation of the mitotic spindle within this plane. In the Drosophila wing disc epithelium, symmetric cell divisions preferentially align with the proximal-distal (PD) axis, thus elongating the organ along this axis (Baena-López et al, 2005). This preferential cell division orientation is determined by the Fat-Dachsous pathway, which promotes