Lin28 Signaling Supports Mammalian PNS and CNS Axon Regeneration

• Main Authors: Xue-Wei Wang, Qiao Li, Chang-Mei Liu, Philip A. Hall, Jing-Jing Jiang, Christopher D. Katchis, Sehwa Kang, Bryan C. Dong, Shuxin Li, Feng-Quan Zhou
• Format: Article
• Language: English
• Published: Elsevier 2018-09-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124718312385

Summary: RNA-binding proteins Lin28a/b regulate cellular growth and tissue regeneration. Here, we investigated the role of Lin28 in the control of axon regeneration in postmitotic neurons. We find that Lin28a/b are both necessary and sufficient for supporting axon regeneration in mature sensory neurons through their regulatory partners, let-7 microRNAs (miRNAs). More importantly, overexpression of Lin28a in mature retinal ganglion cells (RGCs) produces robust and sustained optic nerve regeneration. Additionally, combined overexpression of Lin28a and downregulation of Pten in RGCs act additively to promote optic nerve regeneration, potentially by reducing the backward turning of regenerating RGC axons. Our findings not only reveal a vital role of Lin28 signaling in regulating mammalian axon regeneration but also identify a signaling pathway that can promote axon regeneration in the central nervous system (CNS). : Axon regeneration in the mammalian CNS is a challenge. Wang et al. show that the Lin28/let-7 axis plays an important role in governing mammalian axon regeneration in the peripheral nervous system. More importantly, overexpression of Lin28a induces robust and sustained axon regeneration in the CNS. Keywords: Lin28, axon regeneration, optic nerve regeneration, reprogramming factor, let-7, RNA binding protein, microRNA, sciatic nerve, dorsal root ganglion, retinal ganglion cell