Polarity controls forces governing asymmetric spindle positioning in the Caenorhabditis elegans embryo

Cell divisions that create daughter cells of different sizes are crucial fo r the generation of cell diversity during animal development(1). In such as ymmetric divisions, the mitotic spindle must be asymmetrically positioned a t the end of anaphase(2,3). The mechanisms by which cell polarity translate s to asymmetric spindle positioning remain unclear. Here we examine the nat ure of the forces governing asymmetric spindle positioning in the single-ce ll-stage Caenorhabditis elegans embryo. To reveal the forces that act on ea ch spindle pole, we removed the central spindle in living embryos either ph ysically with an ultraviolet laser microbeam, or genetically by RNA-mediate d interference of a kinesin(4). We show that pulling forces external to the spindle act on the two spindle poles. A stronger net force acts on the pos terior pole, thereby explaining the overall posterior displacement seen in wild-type embryos. We also show that the net force acting on each spindle p ole is under control of the par genes that are required for cell polarity a long the anterior-posterior embryonic axis. Finally, we discuss simple math ematical models that describe the main features of spindle pole behaviour. Our work suggests a mechanism for generating asymmetry in spindle positioni ng by varying the net pulling force that acts on each spindle pole, thus al lowing for the generation of daughter cells with different sizes.