Research Summary

Dissecting the mechanisms of spindle positioning and elongation in animal cells

Proper positioning and elongation of the mitotic spindle are critical steps for determining the correct placement of the cytokinetic furrow. These processes further ensure that the cell fate determinants are appropriately segregated in the newly formed daughter cells during asymmetric cell division, including in stem cells. Evidence from different model systems indicates that spindle positioning is often dictated by an evolutionarily-conserved ternary complex (NuMA/LGN/Gαi1-3 in Homo sapiens and LIN-5/GPR-1/2/Gα in Caenorhabditis elegans). This complex promotes the binding of dynein, the minus-end directed motor protein complex, at the cell cortex. Such cortically anchored dynein is thought to regulate spindle positioning by exerting a pulling force on the plus-end of astral microtubules. Despite our basic understanding regarding the key players involved in spindle positioning, the mechanisms that spatially and temporarily regulate cortical levels of the ternary complex and/or dynein, as cells progress through mitosis, are not well delineated.  Keen interest of my laboratory is to understand the mechanistic insights of spatiotemporal regulation of spindle positioning and spindle elongation by identifying novel components involved in modulating the cortical levels of the ternary complex components and dynein, as well as dynein activity, in time and space. 

Figure Legend: Upper panel is showing still images of C. elegans embryo expressing GFP-PH (membrane marker) and GFP-alpha-tubulin in metaphase (left), anaphase (middle) and two-cell stage (right) C. elegans embryo. Lower panel is illustrating a human cell expressing mCherry-H2B and GFP-alpha-tubulin undergoing mitotic progression from metaphase to anaphase. Note the dynamic nature of these events in both cellular systems.