Phenotypical Analysis of Atypical PKCs In Vivo Function Display a Compensatory System at Mouse Embryonic Day 7.5

Background: The atypical protein kinases C (PKC) isoforms iota/lambda and zeta play crucial roles in many cellular processes including development, cell proliferation, differentiation and cell survival. Possible redundancy between the two isoforms has always been an issue since most biochemical tools do not differentiate between the two proteins. Thus, much effort has been made during the last decades to characterize the functions of aPKCs using gene targeting approaches and depletion studies. However, little is known about the specific roles of each isoform in mouse development. Methodology/Principal Findings: To evaluate the importance of PKC iota in mouse development we designed PKC iota deletion mutants using the gene targeting approach. We show that the deletion of PKC iota, results in a reduced size of the amniotic cavity at E7.5 and impaired growth of the embryo at E8.5 with subsequent absorption of the embryo. Our data also indicate an impaired localization of ZO-1 and disorganized structure of the epithelial tissue in the embryo. Importantly, using electron microscopy, embryoid body formation and immunofluorescence analysis, we found, that in the absence of PKC iota, tight junctions and apico-basal polarity were still established. Finally, our study points to a non-redundant PKC iota function at E9.5, since expression of PKC zeta is able to rescue the E7.5 phenotype, but could not prevent embryonic lethality at a later time-point (E9.5). Conclusion: Our data show that PKC iota is crucial for mouse embryogenesis but is dispensable for the establishment of polarity and tight junction formation. We present a compensatory function of PKC zeta at E7.5, rescuing the phenotype. Furthermore, this study indicates at least one specific, yet unknown, PKC iota function that cannot be compensated by the overexpression of PKC zeta at E9.5.