Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117582
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Type: Journal article
Title: The APC activator fizzy-related-1 (FZR1) is needed for preimplantation mouse embryo development
Author: Seah, M.
Holt, J.
García-Higuera, I.
Moreno, S.
Jones, K.
Citation: Journal of Cell Science, 2012; 125(24):6030-6037
Publisher: Company of Biologists
Issue Date: 2012
ISSN: 0021-9533
1477-9137
Statement of
Responsibility: 
Michelle K. Y. Seah, Janet E. Holt, Irene García-Higuera, Sergio Moreno and Keith T. Jones
Abstract: In early embryos of a number of species the anaphase-promoting complex (APC), an important cell cycle regulator, requires only CDC20 for cell division. In contrast, fizzy-related-1 (FZR1), a non-essential protein in many cell types, is thought to play a role in APC activation at later cell cycles, and especially in endoreduplication. In keeping with this, Fzr1 knockout mouse embryos show normal preimplantation development but die due to a lack of endoreduplication needed for placentation. However, interpretation of the role of FZR1 during this period is hindered by the presence of maternal stores. In this study, therefore, we used an oocyte-specific knockout to examine FZR1 function in early mouse embryo development. Maternal FZR1 was not crucial for completion of meiosis, and furthermore viable pups were born to Fzr1 knockout females mated with normal males. However, in early embryos the absence of both maternal and paternal FZR1 led to a dramatic loss in genome integrity, such that the majority of embryos arrested having undergone only a single mitotic division and contained many γ-H2AX foci, consistent with fragmented DNA. A prominent feature of such embryos was the establishment of two independent spindles following pronuclear fusion and thus a failure of the chromosomes to mix (syngamy). These generated binucleate 2-cell embryos. In the 10% of embryos that progressed to the 4-cell stage, division was so slow that compaction occurred prematurely. No embryo development to the blastocyst stage was ever observed. We conclude that Fzr1 is a surprisingly essential gene involved in the establishment of a single spindle from the two pronuclei in 1-cell embryos as well as being involved in the maintenance of genomic integrity during the mitotic divisions of early mammalian embryos.
Keywords: Mammalian embryos; meiosis; oocytes, mitosis; syngamy; compaction
Rights: © 2012. Published by The Company of Biologists Ltd
RMID: 0030095198
DOI: 10.1242/jcs.110155
Grant ID: http://purl.org/au-research/grants/nhmrc/569202
Appears in Collections:Medical Sciences publications

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