title: Inactivation of aPKClambda reveals a context dependent allocation of cell lineages in preimplantation mouse embryos.
abstract: BACKGROUND
  During mammalian preimplantation development, lineage divergence seems to be controlled by the interplay between asymmetric cell division (once cells are polarized) and positional information. In the mouse embryo, two distinct cell populations are first observed at the 16-cell stage and can be distinguished by both their position (outside or inside) and their phenotype (polarized or non-polarized). Many efforts have been made during the last decade to characterize the molecular mechanisms driving lineage divergence.
  
  
  RESULTS
  In order to evaluate the importance of cell polarity in the determination of cell fate we have disturbed the activity of the apical complex aPKC/PAR6 using siRNA to down-regulate aPKClambda expression. Here we show that depletion of aPKClambda results in an absence of tight junctions and in severe polarity defects at the 16-cell stage. Importantly, we found that, in absence of aPKClambda, cell fate depends on the cellular context: depletion of aPKClambda in all cells results in a strong reduction of inner cells at the 16-cell stage, while inhibition of aPKClambda in only half of the embryo biases the progeny of aPKClambda defective blastomeres towards the inner cell mass. Finally, our study points to a role of cell shape in controlling cell position and thus lineage allocation.
  
  
  CONCLUSIONS
  Our data show that aPKClambda is dispensable for the establishment of polarity at the 8-cell stage but is essential for the stabilization of cell polarity at the 16-cell stage and for cell positioning. Moreover, this study reveals that in addition to positional information and asymmetric cell divisions, cell shape plays an important role for the control of lineage divergence during mouse preimplantation development. Cell shape is able to influence both the type of division (symmetric or asymmetric) and the position of the blastomeres within the embryo.
authors.affiliation: CNRS, UMR7622 - Laboratoire de Biologie Cellulaire du Développement, 9 Quai Saint-Bernard, Bâtiment C, Paris, France. nicolas.dard@upmc.fr
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dard
authors.forename: Tran
authors.initials: T
authors.lastname: Le
authors.forename: Bernard
authors.initials: B
authors.lastname: Maro
authors.forename: Sophie
authors.initials: S
authors.lastname: Louvet-Vallée
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism*; D019070:Cell Lineage; D016764:Cell Polarity; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D018715:Microscopy, Video / Q000379:methods; D008938:Mitosis; D011493:Protein Kinase C / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions; D000099293:Protein Kinase C-lambda
chemical_list: D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011493:Protein Kinase C; D012333:RNA, Messenger; D000099293:Protein Kinase C-lambda