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HORÁKOVÁ, Adéla, Markéta KONEČNÁ, Lenka RADONOVA and Martin ANGER. Early onset of APC/C activity renders SAC inefficient in mouse embryos. Frontiers in Cell and Developmental Biology. Frontiers Media SA, 2024, vol. 12, March 2024, p. 1-13. ISSN 2296-634X. Available from: https://dx.doi.org/10.3389/fcell.2024.1355979.

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TY  - JOUR
ID  - 2387601
AU  - Horáková, Adéla - Konečná, Markéta - Radonova, Lenka - Anger, Martin
PY  - 2024
TI  - Early onset of APC/C activity renders SAC inefficient in mouse embryos
JF  - Frontiers in Cell and Developmental Biology
VL  - 12
IS  - March 2024
SP  - 1-13
EP  - 1-13
PB  - Frontiers Media SA
SN  - 2296634X
KW  - spindle
KW  - spindle assembly checkpoint
KW  - chromosome segregation
KW  - anaphase
KW  - embryo
KW  - Mad1
KW  - anaphase-promoting complex
UR  - https://www.frontiersin.org/articles/10.3389/fcell.2024.1355979/full
N2  - Control mechanisms of spindle assembly and chromosome segregation are vital for preventing aneuploidy during cell division. The mammalian germ cells and embryos are prone to chromosome segregation errors, and the resulting aneuploidy is a major cause of termination of development or severe developmental disorders. Here we focused on early mouse embryos, and using combination of methods involving microinjection, immunodetection and confocal live cell imaging, we concentrated on the Spindle Assembly Checkpoint (SAC) and Anaphase Promoting Complex/Cyclosome (APC/C). These are two important mechanisms cooperating during mitosis to ensure accurate chromosome segregation, and assessed their activity during the first two mitoses after fertilization. Our results showed, that in zygotes and 2-cell embryos, the SAC core protein Mad1 shows very low levels on kinetochores in comparison to oocytes and its interaction with chromosomes is restricted to a short time interval after nuclear membrane disassembly (NEBD). Exposure of 2-cell embryos to low levels of spindle poison does not prevent anaphase, despite the spindle damage induced by the drug. Lastly, the APC/C is activated coincidentally with NEBD before the spindle assembly completion. This early onset of APC/C activity, together with precocious relocalization of Mad1 from chromosomes, prevents proper surveillance of spindle assembly by SAC. The results contribute to the understanding of the origin of aneuploidy in early embryos.
ER  -

Basic information
Original name	Early onset of APC/C activity renders SAC inefficient in mouse embryos
Authors	HORÁKOVÁ, Adéla (203 Czech Republic, belonging to the institution), Markéta KONEČNÁ (203 Czech Republic, belonging to the institution), Lenka RADONOVA and Martin ANGER (203 Czech Republic).
Edition	Frontiers in Cell and Developmental Biology, Frontiers Media SA, 2024, 2296-634X.

Other information
Original language	English
Type of outcome	Article in a journal
Field of Study	10604 Reproductive biology
Country of publisher	Switzerland
Confidentiality degree	is not subject to a state or trade secret
WWW	URL
Impact factor	Impact factor: 5.500 in 2022
Organization unit	Faculty of Science
Doi	http://dx.doi.org/10.3389/fcell.2024.1355979
UT WoS	001190896200001
Keywords in English	spindle; spindle assembly checkpoint; chromosome segregation; anaphase; embryo; Mad1; anaphase-promoting complex
Tags	rivok
Tags	International impact, Reviewed
Changed by	Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 5/4/2024 13:22.

Abstract
Control mechanisms of spindle assembly and chromosome segregation are vital for preventing aneuploidy during cell division. The mammalian germ cells and embryos are prone to chromosome segregation errors, and the resulting aneuploidy is a major cause of termination of development or severe developmental disorders. Here we focused on early mouse embryos, and using combination of methods involving microinjection, immunodetection and confocal live cell imaging, we concentrated on the Spindle Assembly Checkpoint (SAC) and Anaphase Promoting Complex/Cyclosome (APC/C). These are two important mechanisms cooperating during mitosis to ensure accurate chromosome segregation, and assessed their activity during the first two mitoses after fertilization. Our results showed, that in zygotes and 2-cell embryos, the SAC core protein Mad1 shows very low levels on kinetochores in comparison to oocytes and its interaction with chromosomes is restricted to a short time interval after nuclear membrane disassembly (NEBD). Exposure of 2-cell embryos to low levels of spindle poison does not prevent anaphase, despite the spindle damage induced by the drug. Lastly, the APC/C is activated coincidentally with NEBD before the spindle assembly completion. This early onset of APC/C activity, together with precocious relocalization of Mad1 from chromosomes, prevents proper surveillance of spindle assembly by SAC. The results contribute to the understanding of the origin of aneuploidy in early embryos.

Abstract

Control mechanisms of spindle assembly and chromosome segregation are vital for preventing aneuploidy during cell division. The mammalian germ cells and embryos are prone to chromosome segregation errors, and the resulting aneuploidy is a major cause of termination of development or severe developmental disorders. Here we focused on early mouse embryos, and using combination of methods involving microinjection, immunodetection and confocal live cell imaging, we concentrated on the Spindle Assembly Checkpoint (SAC) and Anaphase Promoting Complex/Cyclosome (APC/C). These are two important mechanisms cooperating during mitosis to ensure accurate chromosome segregation, and assessed their activity during the first two mitoses after fertilization. Our results showed, that in zygotes and 2-cell embryos, the SAC core protein Mad1 shows very low levels on kinetochores in comparison to oocytes and its interaction with chromosomes is restricted to a short time interval after nuclear membrane disassembly (NEBD). Exposure of 2-cell embryos to low levels of spindle poison does not prevent anaphase, despite the spindle damage induced by the drug. Lastly, the APC/C is activated coincidentally with NEBD before the spindle assembly completion. This early onset of APC/C activity, together with precocious relocalization of Mad1 from chromosomes, prevents proper surveillance of spindle assembly by SAC. The results contribute to the understanding of the origin of aneuploidy in early embryos.