title: The centrosome orientation checkpoint is germline stem cell specific and operates prior to the spindle assembly checkpoint in Drosophila testis.
abstract: Asymmetric cell division is utilized by a broad range of cell types to generate two daughter cells with distinct cell fates. In stem cell populations asymmetric cell division is believed to be crucial for maintaining tissue homeostasis, failure of which can lead to tissue degeneration or hyperplasia/tumorigenesis. Asymmetric cell divisions also underlie cell fate diversification during development. Accordingly, the mechanisms by which asymmetric cell division is achieved have been extensively studied, although the check points that are in place to protect against potential perturbation of the process are poorly understood. Drosophila melanogaster male germline stem cells (GSCs) possess a checkpoint, termed the centrosome orientation checkpoint (COC), that monitors correct centrosome orientation with respect to the component cells of the niche to ensure asymmetric stem cell division. To our knowledge, the COC is the only checkpoint mechanism identified to date that specializes in monitoring the orientation of cell division in multicellular organisms. Here, by establishing colcemid-induced microtubule depolymerization as a sensitive assay, we examined the characteristics of COC activity and find that it functions uniquely in GSCs but not in their differentiating progeny. We show that the COC operates in the G2 phase of the cell cycle, independently of the spindle assembly checkpoint. This study may provide a framework for identifying and understanding similar mechanisms that might be in place in other asymmetrically dividing cell types.
authors.affiliation: Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA zvenkei@umich.edu yukikomy@umich.edu.
authors.forename: Zsolt G
authors.initials: ZG
authors.lastname: Venkei
authors.affiliation: Life Sciences Institute, Center for Stem Cell Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109-2216, USA Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109-2216, USA zvenkei@umich.edu yukikomy@umich.edu.
authors.forename: Yukiko M
authors.initials: YM
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D018385:Centrosome / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology*; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D059566:M Phase Cell Cycle Checkpoints; D008297:Male; D008870:Microtubules / Q000378:metabolism; D009154:Mutation; D009928:Organ Specificity; D058105:Polymerization; D034622:RNA Interference; D013093:Spermatogonia / Q000166:cytology*; D013737:Testis / Q000166:cytology*
chemical_list: D029721:Drosophila Proteins
keywords: Asymmetric cell division; Centrosome; Checkpoint; Drosophila; Spindle orientation; Stem cells