Grant: Operating Grant

Cell division occurs due to the ingression of a contractile actin-myosin ring, which pinches the mother cell to form two daughter cells. The goal of cell division is to ensure that the daughter cells form with the proper complement of chromosomes and cytosolic components. Failure to do so may be detrimental, for example, cells that inherit the incorrect number of chromosomes will have instable genomes, which can lead to tumour formation. Also, cells without the proper cytosolic components may adopt a different cell fate, which may disrupt the developmental program of an organism. Despite the importance of cell division, we still do not understand the mechanism that defines the division plane. The mitotic spindle is a structure that provides signals to initiate contractile ring formation. One part of the mitotic spindle, the central spindle, forms between segregating chromosomes and provides a stimulatory cue to activate the small GTPase RhoA, the upstream regulator of actin and myosin. We have started to identify some of the molecular components of this pathway, however it is still not clear how they temporally and spatially coordinate RhoA activation. The objective of this proposal is to further understand the regulation of cytoskeletal dynamics during cell division in animal cells, in particular, to understand the mechanism that defines the division plane by restricting the localization of active RhoA to form the contractile ring at the right place and time.