Spindle assembly and chromosome segregation during cell division
Proper segregation of chromosomes during mitosis and meiosis depends upon the formation of a bipolar spindle. In most cell types, duplicated centrosomes contribute to spindle assembly by nucleating microtubules and helping to organize the two poles. However, during meiosis in female animals the centrosomes are degraded prior to the meiotic divisions, and therefore oocyte spindles form in their absence. We are interested in understanding how these acentrosomal spindles form, how they are organized, and how they promote proper chromosome partitioning. To address these questions, we combine high-resolution microscopy with genetic, genomic, and biochemical approaches in the nematode C. elegans.
These studies are important since errors in meiotic chromosome segregation result in aneuploidy, a leading cause of miscarriages and birth defects in humans. Female meiosis in particular is highly error prone and this vulnerability has a profound impact on human health; it is estimated that as many as 10-25% of human embryos are chromosomally abnormal, and the vast majority of these defects arise from problems with the oocytes. Our research will yield a better molecular understanding of the mechanisms that promote accurate chromosome segregation during oocyte meiosis, which will shed light on how genomic integrity is maintained during the meiotic divisions.
Assembly of Caenorhabditis elegans acentrosomal spindles occurs without evident microtubule-organizing centers and requires microtubule sorting by KLP-18/kinesin-12 and MESP-1. Wolff ID, Tran MV, Mullen TJ, Villeneuve AM, and Wignall SM. Molecular Biology of the Cell. 2016 October 15;27(20):3122-3131.
Kinetochore-independent chromosome segregation driven by lateral microtubule bundles. Muscat CC, Torre-Santiago KM, Tran MV, Powers JA, and Wignall SM. eLife. 2015 May 30;4:e06462.
Cell Division: Stem Cells Take the Stage. Wignall SM. Current Biology. 2015 May 4;25(9):R376-R378.
Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes. Schvarzstein M, Wignall SM, and Villeneuve AM. Genes & Development. 2010 February 1;24(3):219-228.
Lateral microtubule bundles promote chromosome alignment during acentrosomal oocyte meiosis. Wignall SM and Villeneuve AM. Nature Cell Biology. 2009 July;11(7):839-844.
Identification of a Novel Protein Regulating Microtubule Stability through a Chemical Approach. Wignall SM, Gray NS, Chang Y-T, Juarez L, Jacob R, Burlingame A, Schultz PG, and Heald R. Chemistry & Biology. 2004 January;11(1):135-146.
The condensin complex is required for proper spindle assembly and chromosome segregation in Xenopus egg extracts. Wignall SM, Deehan R, Maresca TJ, and Heald R. Journal of Cell Biology. 2003 June 23;161(6):1041-1051.
Methods for the study of centrosome-independent spindle assembly in Xenopus extracts. Wignall SM and Heald R. Methods in Cell Biology. 2001;67:241-256.
View all publications by Sarah M. Wignall listed in the National Library of Medicine (PubMed).