Cdk7 Regulates Myelin Sheath Morphology and Lipid Homeostasis in Schwann Cells

Schwann cells (SC) are responsible for myelination in the peripheral nervous system (PNS). Myelin allows saltatory transmission of action potentials along axons and functionally relies on its unique constitution. We previously reported that Cdk7, a regulator of cell cycle progression and transcription, regulates myelin gene expression in oligodendrocytes and contributes to myelin maintenance in the central nervous system. Using mice with conditional Cdk7 knock-out in SCs, we provide evidence that Cdk7 is dispensable for myelin initiation but needed for the correct myelin thickness of larger caliber fibers in young mice, as well as for myelin elongation and rapid nerve conduction throughout age. We report that Cdk7 loss results in disturbed myelin stoichiometry, with significant dysregulation of lipid-related genes in SCs and a reduction in myelin protein zero. Finally, we demonstrate that Rxrγ, a nuclear receptor involved in lipid metabolism, is significantly downregulated in the absence of Cdk7. However, although Cdk7 regulates myelin segment length, our results indicate that this effect occurs independently of Rxrγ in myelinating dorsal root ganglion explants.