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Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo

Plusa, Berenika and Frankenberg, Stephen and Chalmers, Andrew and Hadjantonakis, Anna-Katerina and Moore, Catherine A. and Papalopulu, Nancy and Papaioannou, Virginia E. and Glover, David M. and Zernicka-Goetz, Magdalena (2005) Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo. Journal of Cell Science, 118 (3). pp. 505-515. ISSN 0021-9533. doi:10.1242/jcs.01666. https://resolver.caltech.edu/CaltechAUTHORS:20190419-105738009

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Abstract

Generation of inside cells that develop into inner cell mass (ICM) and outside cells that develop into trophectoderm is central to the development of the early mouse embryo. Critical to this decision is the development of cell polarity and the associated asymmetric (differentiative) divisions of the 8-cell-stage blastomeres. The underlying molecular mechanisms for these events are not understood. As the Par3/aPKC complex has a role in establishing cellular polarity and division orientation in other systems, we explored its potential function in the developing mouse embryo. We show that both Par3 and aPKC adopt a polarized localization from the 8-cell stage onwards and that manipulating their function re-directs cell positioning and consequently influences cell fate. Injection of dsRNA against Par3 or mRNA for a dominant negative form of aPKC into a random blastomere at the 4-cell stage directs progeny of the injected cell into the inside part of the embryo. This appears to result from both an increased frequency by which such cells undertake differentiative divisions and their decreased probability of retaining outside positions. Thus, the natural spatial allocation of blastomere progeny can be over-ridden by downregulation of Par3 or aPKC, leading to a deceased tendency for them to remain outside and so develop into trophectoderm. In addition, this experimental approach illustrates a powerful means of manipulating gene expression in a specific clonal population of cells in the preimplantation embryo.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1242/jcs.01666DOIArticle
http://jcs.biologists.org/cgi/content/full/118/3/505/DC1PublisherSupporting Information
ORCID:
AuthorORCID
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2005 The Company of Biologists. Accepted 29 November 2004. M.Z.G. is grateful to the Wellcome Trust for a Senior Research Fellowship and support from the Human Frontiers Science Program. M.Z.G. and D.M.G. acknowledge support from a BBSRC Project Grant. V.E.P. acknowledges support of NIH Grant R01 GM060561. N.P. acknowledges support from a Senior Wellcome Fellowship and A.C. acknowledges support from an MRC Career Development Fellowship. We thank J. Na for assistance in constructs and in synthesizing dsRNA, F. Wianny for experiments to downregulate E-cadherin, T. Fleming for helpful suggestions and anti-ZO1 antibody, A. Sossick for assistance in image analysis, B. McCabe for advice on statistical analysis, and M. Johnson for helpful discussions.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Human Frontier Science ProgramUNSPECIFIED
Biotechnology and Biological Sciences Research Council (BBSRC)UNSPECIFIED
NIHR01 GM060561
Medical Research Council (UK)UNSPECIFIED
Subject Keywords:Par3, aPKC, Polarity, Preimplantation embryo, Blastomere, Blastocyst formation
Issue or Number:3
DOI:10.1242/jcs.01666
Record Number:CaltechAUTHORS:20190419-105738009
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190419-105738009
Official Citation:Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo Berenika Plusa, Stephen Frankenberg, Andrew Chalmers, Anna-Katerina Hadjantonakis, Catherine A. Moore, Nancy Papalopulu, Virginia E. Papaioannou, David M. Glover, Magdalena Zernicka-Goetz Journal of Cell Science 2005 118: 505-515; doi: 10.1242/jcs.01666
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94820
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:23 Apr 2019 17:08
Last Modified:16 Nov 2021 17:08

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