Citation: Sarah Woolner, Nancy Papalopulu,
Spindle position in symmetric cell divisions during epiboly is controlled by opposing and dynamic apicobasal forces. Developmental cell 22(4): Full text doi:10.1016/j.devcel.2012.01.002
Confocal image of a bisected Xenopus gastrula stage embryo, stained for α-tubulin (red), membrane-GFP (green) and DNA (blue). Cells in the outer epithelium (top) undergo symmetric cell divisions, with their mitotic spindles oriented parallel to the plane of the epithelium.
Oriented cell division is a key tool used to shape tissues and determine cell fate. Whilst much effort has been focused on understanding the basis for asymmetric cell division, we know less about the cellular mechanisms that control symmetric divisions. In epithelium, symmetric divisions – where the cell divides in the plane of the tissue – are crucial for spreading tissue during development and for maintaining tissue architecture in the adult. In order for these divisions to occur, we know that the mitotic spindle must be held perfectly level, but the cellular mechanisms that control this have remained unclear.
To investigate how mitotic spindles are positioned during symmetric divisions, we used the Xenopus embryo where spindles can be followed live in intact epithelial tissue. We studied spindle position in the epithelium of embryos undergoing epiboly, a morphogenetic movement where the embryonic epithelium must spread to cover the embryo. We showed that during epiboly, antagonistic and dynamic apicobasal forces hold mitotic spindles parallel to the plane of the epithelium while allowing planar rotation of the spindle, ensuring even spreading of the epithelial sheet. Specifically, we demonstrated that apical astral microtubules, together with the myosin-10 motor protein, exert a basally directed force on the spindle. When either astral microtubules or myosin-10 are disrupted, the spindle moves apically and loses absolute planar alignment. This basally-directed force is balanced by an apically-directed force, supplied by myosin-2 driven cortical flow of F-actin. When either myosin-2 or F-actin are disrupted, the spindle moves basally and loses absolute planar alignment. In embryos in which both apical and basal forces are disrupted, spindle position varies dramatically and spindles no longer align with the epithelial plane. As a result, the epithelium becomes disorganized.
Unlike other models that invoke anchoring of the spindle to a cortical landmark, our findings support a model of dynamic force interactions that maintain spindle position within the plane of epithelium. Importantly, this mechanism may allow cells to respond to changes in the local environment, such as altered tissue tension, by quickly adjusting the orientation of the mitotic spindle.
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