Abstract:
:Genome integrity in the developing germ line is strictly required for fecundity. In proliferating somatic cells and in germ cells, there are mitotic checkpoint mechanisms that ensure accurate chromosome segregation and euploidy. There is growing evidence of mitotic cell cycle components that are uniquely required in the germ line to ensure genome integrity. We previously showed that the primary phenotype of germ cell deficient 2 (gcd2) mutant mice is infertility due to germ cell depletion during embryogenesis. Here we show that the underlying mutation is a mis-sense mutation, R308K, in the motor domain of the kinesin-8 family member, KIF18A, a protein that is expressed in a variety of proliferative tissues and is a key regulator of chromosome alignment during mitosis. Despite the conservative nature of the mutation, we show that its functional consequences are equivalent to KIF18A deficiency in HeLa cells. We also show that somatic cells progress through mitosis, despite having chromosome alignment defects, while germ cells with similar chromosome alignment defects undergo mitotic arrest and apoptosis. Our data provide evidence for differential requirements for chromosome alignment in germ and somatic cells and show that Kif18a is one of a growing number of genes that are specifically required for cell cycle progression in proliferating germ cells.
journal_name
Dev Bioljournal_title
Developmental biologyauthors
Czechanski A,Kim H,Byers C,Greenstein I,Stumpff J,Reinholdt LGdoi
10.1016/j.ydbio.2015.03.011subject
Has Abstractpub_date
2015-06-15 00:00:00pages
253-262issue
2eissn
0012-1606issn
1095-564Xpii
S0012-1606(15)00144-Xjournal_volume
402pub_type
杂志文章abstract::We describe mesendoderm morphogenesis during gastrulation in the frog Xenopus laevis and investigate the mechanics of these movements with tissue explants. When a dorsal marginal zone explant is plated onto fibronectin, the mesendoderm moves away from the dorsal axial tissues as an intact sheet. Mesendodermal cells wi...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2002.0537
更新日期:2002-02-15 00:00:00
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journal_title:Developmental biology
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2000.9663
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journal_title:Developmental biology
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Developmental biology
pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
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更新日期:2017-11-15 00:00:00
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更新日期:2010-08-15 00:00:00
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pub_type: 杂志文章
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2003.07.010
更新日期:2003-11-15 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.2000.9910
更新日期:2000-11-15 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2004.03.023
更新日期:2004-07-01 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2007.10.042
更新日期:2008-01-15 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1994.1274
更新日期:1994-10-01 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1996.0016
更新日期:1996-01-10 00:00:00
abstract::Gastrulation is the first major morphogenetic movement in development and requires dynamic regulation of cell adhesion and the cytoskeleton. Caenorhabditis elegans gastrulation begins with the migration of the two endodermal precursors, Ea and Ep, from the surface of the embryo into the interior. Ea/Ep migration provi...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2010.05.507
更新日期:2010-08-15 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1996.0073
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更新日期:2018-02-01 00:00:00
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更新日期:1992-06-01 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1006/dbio.1997.8514
更新日期:1997-04-01 00:00:00
abstract::The fertilized ascidian egg is thought to be comprised of distinct regions of tissue-specific cytoplasmic determinants. This idea was tested by bisecting fertilized eggs into egg fragments and culturing them until the unoperated controls developed into larvae. Fertilized eggs were bisected using a microsurgical method...
journal_title:Developmental biology
pub_type: 杂志文章
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更新日期:1988-09-01 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2010.04.016
更新日期:2010-07-01 00:00:00
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journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2011.02.015
更新日期:2011-05-01 00:00:00
abstract::Early embryonic cells are capable of acquiring numerous developmental fates until they become irreversibly committed to specific lineages depending on intrinsic determinants and/or regional interactions. From fertilization to gastrulation, such pluripotent cells first increase in number and then turn to undergoing dif...
journal_title:Developmental biology
pub_type: 杂志文章,评审
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更新日期:2019-08-15 00:00:00
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journal_title:Developmental biology
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更新日期:2009-04-01 00:00:00
abstract::In amphibians, the composition and pattern of expression of the myosin heavy chain (myHC) gene family are mostly unknown. To understand better the regulation of this complex family, we screened cDNA libraries from swimming tadpole and adult leg muscle RNA and have isolated and partially sequenced clones for several my...
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pub_type: 杂志文章
doi:10.1016/0012-1606(89)90058-4
更新日期:1989-06-01 00:00:00
abstract::FoxC, FoxF, FoxL1 and FoxQ1 genes have been shown to be clustered in some animal genomes, with mesendodermal expression hypothesised as a selective force maintaining cluster integrity. Hypotheses are, however, constrained by a lack of data from the Lophotrochozoa. Here we characterise members of the FoxC, FoxF, FoxL1 ...
journal_title:Developmental biology
pub_type: 杂志文章
doi:10.1016/j.ydbio.2010.01.015
更新日期:2010-04-15 00:00:00