@article{9afa9f8467694919b477fb2d7c73dcf3,
title = "Knocking Out Non-muscle Myosin II in Retinal Ganglion Cells Promotes Long-Distance Optic Nerve Regeneration",
abstract = "In addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here, we show that knocking out myosin IIA and IIB (myosin IIA/B) in retinal ganglion cells alone, either before or after optic nerve crush, induces significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout lead to an additive promoting effect and long-distance axon regeneration. Immunostaining, RNA sequencing, and western blot analyses reveal that myosin II deletion does not affect known axon regeneration signaling pathways or the expression of regeneration-associated genes. Instead, it abolishes the retraction bulb formation and significantly enhances the axon extension efficiency. The study provides clear evidence that directly targeting neuronal cytoskeleton is sufficient to induce significant CNS axon regeneration and that combining altered gene expression in the soma and modified cytoskeletal dynamics in the axon is a promising approach for long-distance CNS axon regeneration.",
keywords = "Lin28, axon regeneration, cytoskeleton, growth cone, non-muscle myosin II, optic nerve regeneration, post-injury treatment, retinal ganglion cells, retraction bulb",
author = "Wang, {Xue Wei} and Yang, {Shu Guang} and Chi Zhang and Hu, {Ming Wen} and Jiang Qian and Ma, {Jin Jin} and Yingchi Zhang and Yang, {Bin Bin} and Weng, {Yi Lan} and Ming, {Guo Li} and Kosanam, {Anish R.} and Saijilafu and Zhou, {Feng Quan}",
note = "Funding Information: We acknowledge Dr. Michele Pucak from the Multiphoton Imaging Core (supported by NS050274) of the Department of Neuroscience, Johns Hopkins School of Medicine for her help in confocal microscopy. We thank Hao Zhang from the Flow Cytometry Cell Sorting Core Facility at Bloomberg School of Public Health, Johns Hopkins University for doing FACS sorting. The facility was supported by 1S10OD016315-01 and 1S10RR13777001 and, in part, by CFAR: 5P30AI094189-04 (Chaisson). We appreciate the Johns Hopkins Transcriptomics and Deep Sequencing Core for doing the RGC RNA-seq experiment. We also thank Ying Zhang for drawing the graphical abstract. The study was supported by grants (to F.-Q.Z. and J.Q.) from NIH (R01NS064288, R01NS085176, R01GM111514, R01EY027347, and R01EY029548), the Craig H. Neilsen Foundation (259450), and the BrightFocus Foundation (G2017037). S. was supported by the grants from the National Natural Science Foundation of China (81571189 and 81772353), the National Key Research and Development Program (2016YFC1100203), and Innovation and Entrepreneurship Program of Jiangsu Province. X.-W.W. S.-G.Y. S. and F.-Q.Z. conceived the study and designed the project; X.-W.W. and S.-G.Y. performed most of the experiments; X.-W.W. and C.Z. performed and analyzed the immunostaining and western blot experiments; M.-W.H. and J.Q. analyzed the RGC RNA-seq data; Y.Z. analyzed optic nerve regeneration; C.Z. and Y.Z. analyzed the axon morphologies and trajectories; J.-J.M. performed the DRG RNA-seq experiment; Y.-L.W. and G.-L.M. helped with the optic nerve regeneration experiments; B.-B.Y. and A.R.K. helped with the data analyses; X.-W.W. and F.-Q.Z. wrote the manuscript with contributions from all authors. The authors declare no competing financial interests. Funding Information: We acknowledge Dr. Michele Pucak from the Multiphoton Imaging Core (supported by NS050274) of the Department of Neuroscience, Johns Hopkins School of Medicine for her help in confocal microscopy. We thank Hao Zhang from the Flow Cytometry Cell Sorting Core Facility at Bloomberg School of Public Health, Johns Hopkins University for doing FACS sorting. The facility was supported by 1S10OD016315-01 and 1S10RR13777001 and, in part, by CFAR : 5P30AI094189-04 (Chaisson). We appreciate the Johns Hopkins Transcriptomics and Deep Sequencing Core for doing the RGC RNA-seq experiment. We also thank Ying Zhang for drawing the graphical abstract. The study was supported by grants (to F.-Q.Z. and J.Q.) from NIH ( R01NS064288 , R01NS085176 , R01GM111514 , R01EY027347 , and R01EY029548 ), the Craig H. Neilsen Foundation ( 259450 ), and the BrightFocus Foundation ( G2017037 ). S. was supported by the grants from the National Natural Science Foundation of China ( 81571189 and 81772353 ), the National Key Research and Development Program ( 2016YFC1100203 ), and Innovation and Entrepreneurship Program of Jiangsu Province . Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = apr,
day = "21",
doi = "10.1016/j.celrep.2020.107537",
language = "English (US)",
volume = "31",
pages = "107537",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}