title: The zebra fish cassiopeia mutant reveals that SIL is required for mitotic spindle organization.
abstract: A critical step in cell division is formation of the mitotic spindle, which is a bipolar array of microtubules that mediates chromosome separation. Here, we report that the SCL-interrupting locus (SIL), a vertebrate-specific cytosolic protein, is necessary for proper mitotic spindle organization in zebrafish and human cells. A homozygous lethal zebrafish mutant, cassiopeia (csp), was identified by a genetic screen for mitotic mutant. csp mutant embryos have an increased mitotic index, have highly disorganized mitotic spindles, and often lack one or both centrosomes. These phenotypes are caused by a loss-of-function mutation in zebrafish sil. To determine if the requirement for SIL in mitotic spindle organization is conserved in mammals, we generated an antibody against human SIL, which revealed that SIL localizes to the poles of the mitotic spindle during metaphase. Furthermore, short hairpin RNA knockdown of SIL in human cells recapitulates the zebrafish csp mitotic spindle defects. These data, taken together, identify SIL as a novel, vertebrate-specific regulator of mitotic spindle assembly.
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston, Dana Farber Cancer Research Institute, Howard Hughes Medical Institute, and Harvard Medical School, Karp Family Research Building, Boston, Massachusetts 02115, USA.
authors.forename: Kathleen L
authors.initials: KL
authors.lastname: Pfaff
authors.forename: Christian T
authors.initials: CT
authors.lastname: Straub
authors.forename: Ken
authors.initials: K
authors.lastname: Chiang
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Bear
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D019521:Body Patterning; D018797:Cell Cycle Proteins / Q000378:metabolism*; D000072159:Dynactin Complex; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D000072159:Dynactin Complex; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C071236:STIL protein, human; C522344:Stil protein, zebrafish; D029961:Zebrafish Proteins