During the first meiotic division, homologous chromosomes linked by chiasmata interact with the spindle microtubules and segregate to opposite poles. Defects in this process lead to aneuploidy in the fertilized egg and have serious consequences on development, often resulting in death of the developing embryo. In humans, aneuploidy is a leading cause of spontaneous abortions and infertility in women. If aneuploids do survive, they manifest with diseases such as Down's, Tumer's or Klinefelter's syndrome. In many organisms, including humans and flies, the female meiotic spindle lacks centrioles and the classical microtubule-organizing center at the poles. The centrosomes and their constituent proteins are usually thought to organize bipolar spindles and therefore, in female meiosis, spindle pole organization must occur by a novel mechanism. By utilizing the powerful genetic and cytological techniques available in studies involving Drosophila melanogaster females, it is our long-term goal to elucidate the mechanism by which acentrosomal meiotic spindles form and how they function to segregate the chromosomes. We have found that the subito (sub) gene is required for bipolar spindle formation and homolog segregation during female meiosis in Drosophila. The findings that sub encodes a kinesin-like motor protein and is required during early embryogenesis and male meiosis has stimulated several new experiments.
The aims of this study are to identify the role of SUB in spindle formation and understand how the meiotic spindle forms and functions to segregate chromosomes in the absence of centrosomes. A combination of genetic, immunological and cytological techniques will be used to illuminate the functions of SUB. These studies will investigate three critical areas of spindle biology by: 1) determining the subcellular localization of the sub protein in meiotic spindles and characterize how SUB interacts with the microtubules, 2) determining what other proteins interacts with SUB, and 3) using live imaging techniques to investigate the mechanism of spindle pole formation through a real time analysis of meiosis and mitosis in wild-type and mutants. The results of these studies will provide insights into the mechanisms of spindle formation and homolog segregation during meiosis and mitosis.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Reproductive Biology Study Section (REB)
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Deatherage, James F
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Rutgers University
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New Brunswick
United States
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Radford, Sarah J; Jang, Janet K; McKim, Kim S (2012) The chromosomal passenger complex is required for meiotic acentrosomal spindle assembly and chromosome biorientation. Genetics 192:417-29
Radford, Sarah J; Harrison, Andrew M; McKim, Kim S (2012) Microtubule-depolymerizing kinesin KLP10A restricts the length of the acentrosomal meiotic spindle in Drosophila females. Genetics 192:431-40
Cesario, J; McKim, K S (2011) RanGTP is required for meiotic spindle organization and the initiation of embryonic development in Drosophila. J Cell Sci 124:3797-810
McKim, Kim S; Joyce, Eric F; Jang, Janet K (2009) Cytological analysis of meiosis in fixed Drosophila ovaries. Methods Mol Biol 558:197-216
Wu, Changjian; Singaram, Vinod; McKim, Kim S (2008) mei-38 is required for chromosome segregation during meiosis in Drosophila females. Genetics 180:61-72
Colombie, Nathalie; Cullen, C Fiona; Brittle, Amy L et al. (2008) Dual roles of Incenp crucial to the assembly of the acentrosomal metaphase spindle in female meiosis. Development 135:3239-46
Jang, Janet K; Rahman, Taslima; Kober, Vanessa S et al. (2007) Misregulation of the kinesin-like protein Subito induces meiotic spindle formation in the absence of chromosomes and centrosomes. Genetics 177:267-80
Doubilet, Susan; McKim, Kim S (2007) Spindle assembly in the oocytes of mouse and Drosophila--similar solutions to a problem. Chromosome Res 15:681-96
Cesario, Jeff M; Jang, Janet K; Redding, Bethany et al. (2006) Kinesin 6 family member Subito participates in mitotic spindle assembly and interacts with mitotic regulators. J Cell Sci 119:4770-80
Horner, Vanessa L; Czank, Andreas; Jang, Janet K et al. (2006) The Drosophila calcipressin sarah is required for several aspects of egg activation. Curr Biol 16:1441-6

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