Searching across hundreds of databases
Chromosome segregation errors during mammalian preimplantation development cause "mosaic" embryos comprising a mixture of euploid and aneuploid cells, which reduce the potential for a successful pregnancy [1-5], but why these errors are common is unknown. In most cells, chromosome segregation error is averted by the spindle assembly checkpoint (SAC), which prevents anaphase-promoting complex (APC/C) activation and anaphase onset until chromosomes are aligned with kinetochores attached to spindle microtubules [6, 7], but little is known about the SAC's role in the early mammalian embryo. In C. elegans, the SAC is weak in early embryos, and it strengthens during early embryogenesis as a result of progressively lessening cell size [8, 9]. Here, using live imaging, micromanipulation, gene knockdown, and pharmacological approaches, we show that this is not the case in mammalian embryos. Misaligned chromosomes in the early mouse embryo can recruit SAC components to mount a checkpoint signal, but this signal fails to prevent anaphase onset, leading to high levels of chromosome segregation error. We find that failure of the SAC to prolong mitosis is not attributable to cell size. We show that mild chemical inhibition of APC/C can extend mitosis, thereby allowing more time for correct chromosome alignment and reducing segregation errors. SAC-APC/C disconnect thus presents a mechanistic explanation for frequent chromosome segregation errors in early mammalian embryos. Moreover, our data provide proof of principle that modulation of the SAC-APC/C axis can increase the likelihood of error-free chromosome segregation in cultured mammalian embryos.
Pubmed ID: 30773364 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis monoclonal targets beta-Tubulin
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
scicrunch.org
