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First published online 18 January 2005
doi: 10.1242/jcs.01666

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

Berenika Plusa^1,3,*,, Stephen Frankenberg^1,3,*, Andrew Chalmers^1,5, Anna-Katerina Hadjantonakis^4,, Catherine A. Moore^1,3, Nancy Papalopulu^1,5, Virginia E. Papaioannou⁴, David M. Glover^2,3 and Magdalena Zernicka-Goetz^1,3,¶

¹ Wellcome Trust and Cancer Research UK Gurdon Institute, Tennis Court Road, Cambridge CB2 1QR, UK
² Cancer Research UK Cell Cycle Genetics Research Group, Downing Street, Cambridge CB2 3EH, UK
³ Department of Genetics, Downing Street, Cambridge CB2 3EH, UK
⁴ Department of Genetics and Development, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, New York, NY 10032, USA
⁵ Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK

^¶ Author for correspondence (e-mail: mzg{at}mole.bio.cam.ac.uk)

Accepted 29 November 2004

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.

Key words: Par3, aPKC, Polarity, Preimplantation embryo, Blastomere, Blastocyst formation

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