Novel role of Lin28 signaling in regulation of mammalian PNS and CNS axon regeneration

Summary Several signaling molecules involved in cellular reprogramming have been shown to regulate mammalian axon regeneration. We hypothesized that reprogramming factors are key regulators of axon regeneration. Here we investigated the role of Lin28, an important reprogramming factor, in the regulation of axon regeneration. We found that Lin28a and Lin28b and their regulatory partners, let-7 microRNAs (miRNAs), were both necessary and sufficient in regulating mature sensory axon regeneration in vivo. More importantly, overexpression of either Lin28a or Lin28b in mature retinal ganglion cells (RGCs) promoted robust and sustained optic nerve regeneration. Additionally, combined overexpression of Lin28a and downregulation of PTEN in RGCs acted additively to promote optic nerve regeneration by reducing the backward turning of regenerating RGC axons. Our findings not only identified a novel molecule promoting optic nerve regeneration but also suggested that reprogramming factors may play vital roles in regulating axon regeneration in mammals.