The protocadherin alpha cluster is required for axon extension and myelination in the developing central nervous system

In adult mammals,axon regeneration after central nervous system injury is very poor,resulting in persistent functional loss.Enhancing the ability of axonal outgrowth may be a potential treatment strategy because mature neurons of the adult central nervous system may retain the intrinsic ability to regrow axons after injury.The protocadherin(Pcdh)clusters are thought to function in neuronal morphogenesis and in the assembly of neural circuitry in the brain.We cultured primary hippocampal neurons from E17.5 Pcdhαdeletion(del-α)mouse embryos.After culture for 1 day,axon length was obviously shorter in del-αneurons compared with wild-type neurons.RNA sequencing of hippocampal E17.5 RNA showed that expression levels of BDNF,Fmod,Nrp2,OGN,and Sema3d,which are associated with axon extension,were significantly down-regulated in the absence of the Pcdhαgene cluster.Using transmission electron microscopy,the ratio of myelinated nerve fibers in the axons of del-αhippocampal neurons was significantly decreased;myelin sheaths of P21 Pcdhα-del mice showed lamellar disorder,discrete appearance,and vacuoles.These results indicate that the Pcdhαcluster can promote the growth and myelination of axons in the neurodevelopmental stage.