Cdk7 regulates peripheral myelin sheath extension and lipid content.

Myelin allows saltatory transmission of action potentials along axons and functionally relies on its unique constitution. Schwann cells (SC) are the glial cells responsible for myelination in the peripheral nervous system (PNS), and their differentiation constitutes a stepwise process involving accurate coordination of proliferation and fine-tuned gene expression.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 adult central nervous system. Using conditional Cdk7 knock-out mice, we provide evidence that Cdk7 is not required for myelin initiation but is needed for the correct rate of myelination of larger calibre fibres, as well as for myelin elongation and rapid nerve conduction. We show that Cdk7 loss results in significant dysregulation of lipid-related genes in SCs in addition to a reduction in myelin protein zero, leading to disturbed myelin stoichiometry. Finally, we show that Rxrγ, a nuclear receptor involved in lipid metabolism, is downregulated in the absence of Cdk7 and that Cdk7 is required for the myelination-promoting effect of Rxrγ in myelinating dorsal root ganglion explants.