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Development November 1, 2013; 140 (21): 4311-22.

Atypical protein kinase C couples cell sorting with primitive endoderm maturation in the mouse blastocyst.

Saiz N , Grabarek JB , Sabherwal N , Papalopulu N , Plusa B .

During mouse pre-implantation development, extra-embryonic primitive endoderm (PrE) and pluripotent epiblast precursors are specified in the inner cell mass (ICM) of the early blastocyst in a ''salt and pepper'' manner, and are subsequently sorted into two distinct layers. Positional cues provided by the blastocyst cavity are thought to be instrumental for cell sorting; however, the sequence of events and the mechanisms that control this segregation remain unknown. Here, we show that atypical protein kinase C (aPKC), a protein associated with apicobasal polarity, is specifically enriched in PrE precursors in the ICM prior to cell sorting and prior to overt signs of cell polarisation. aPKC adopts a polarised localisation in PrE cells only after they reach the blastocyst cavity and form a mature epithelium, in a process that is dependent on FGF signalling. To assess the role of aPKC in PrE formation, we interfered with its activity using either chemical inhibition or RNAi knockdown. We show that inhibition of aPKC from the mid blastocyst stage not only prevents sorting of PrE precursors into a polarised monolayer but concomitantly affects the maturation of PrE precursors. Our results suggest that the processes of PrE and epiblast segregation, and cell fate progression are interdependent, and place aPKC as a central player in the segregation of epiblast and PrE progenitors in the mouse blastocyst.

PubMed ID: 24067354
PMC ID: PMC4007710
Article link: Development
Grant support: [+]
Genes referenced: cdh1 dab2 fgf4 gata4 gata6 h2bc21 lrp2 mapk1 pdgfra pou5f3.1 prkci

Article Images: [+] show captions
References [+] :
Arman, Targeted disruption of fibroblast growth factor (FGF) receptor 2 suggests a role for FGF signaling in pregastrulation mammalian development. 1998, Pubmed

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