Time-resolved function of cell polarity kinases PRKCZ and PRKCI in CNS myelination [bulk_oligo]

The atypical Protein Kinase C (aPKC) is a critical component of the PAR polarity complex, as well as of cell polarity in general. There are two paralogs of aPKC in the mammalian genome. Their expression pattern and functional role in oligodendrocyte lineage differentiation and development remains heretofore uncharacterized. Here we show that both paralogs of aPKC – PRKCI, the primary transcript of Prkci and PKMz, an alternate transcript of Prkcz – are expressed during oligodendrocyte differentiation, yet are functionally non-redundant. Asymmetric cell division and early specification of the oligodendrocyte fate stage required both paralogs. By contrast, the stage of oligodendrocyte maturation involving membrane polarization and myelination of axons continued to require PKMz, but no longer needed PRKCI. Taken together, our results indicate to a two-stage role of aPKCs and cell polarity in oligodendrocyte differentiation and development. Overall design: To understand the effects of aPKC paralogs in OL lineage development, we performed bulk RNA sequencing of cerebral cortices from Control and Prkci f/f and Prkcz f/f mice crossed with Ng2-cre+ at P30. (3-4 biological replicates for each genotype)