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

Néstor Saiz, Joanna B. Grabarek, Nitin Sabherwal, Nancy Papalopulu, Berenika Plusa

    Research output: Contribution to journalArticlepeer-review


    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. © 2013.
    Original languageEnglish
    Pages (from-to)4311-4322
    Number of pages11
    Issue number21
    Publication statusPublished - 1 Nov 2013


    • aPKC
    • Epiblast
    • GATA4
    • ICM
    • Lineage specification
    • Mouse blastocyst
    • Pluripotency
    • Primitive endoderm


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