Mechanisms of Asymmetric Spindle Positioning in the One-Cell C. elegans Embryo

Asymmetric cell divisions are essential for creating cell diversity in many developing organisms. Cells divide asymmetrically by generating daughter cells of different sizes and/or by unequally partitioning cell-fate determinants.

The first division in the C. elegans embryo shows both of these characteristics. During this division, forces exerted on the microtubules aid in positioning the mitotic spindle toward the posterior of the embryo, leading to an asymmetric division plane. Some key modulators that have been implicated in the initiation and regulation of these asymmetrically distributed forces include cortically localized PAR proteins, receptor independent G-protein signaling, and the microtubule motor protein dynein. While many of the players involved in asymmetric spindle positioning have been identified, the mechanisms behind the forces required for the spindle to shift are not completely understood. Labbé et al. 2003 and Kozlowski et al. 2007 have previously shown that microtubule plus-end residence times at the cortex are longer on the anterior half of the one-cell embryo when compared to the posterior half. These residence times become symmetric in both halves of the embryo in polarity-defective and spindle positioning-defective backgrounds. From this evidence, it has been hypothesized that differential regulation of microtubule stability at the cortex might play a role in asymmetric spindle positioning.

Currently, I am developing reagents and imaging methods that will aid in testing this hypothesis and help elucidate the mechanism behind force generation during the time of the spindle shift.