Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract

作者: M. G. Blackmore , Z. Wang , J. K. Lerch , D. Motti , Y. P. Zhang

DOI: 10.1073/PNAS.1120684109

关键词:

摘要: Axon regeneration in the central nervous system normally fails, part because of a developmental decline intrinsic ability CNS projection neurons to extend axons. Members KLF family transcription factors regulate regenerative potential developing neurons. Expression one member, KLF7, is down-regulated developmentally, and overexpression KLF7 cortical vitro promotes axonal growth. To circumvent difficulties achieving high neuronal expression exogenous we created chimera with VP16 transactivation domain, which displayed enhanced compared native protein while maintaining transcriptional activation growth promotion vitro. Overexpression VP16-KLF7 overcame loss slice cultures. Adult corticospinal tract (CST) failed up-regulate response axon injury, vivo promoted both sprouting CST adult mice. These findings identify unique means promoting by reengineering developmentally down-regulated, growth-promoting factor.

参考文章(55)
Eric A. Huebner, Stephen M. Strittmatter, Axon regeneration in the peripheral and central nervous systems. Results and problems in cell differentiation. ,vol. 48, pp. 339- 351 ,(2009) , 10.1007/400_2009_19
Howard M. Bomze, Ketan R. Bulsara, Bermans J. Iskandar, Pico Caroni, J. H. Pate Skene, Spinal axon regeneration evoked by replacing two growth cone proteins in adult neurons. Nature Neuroscience. ,vol. 4, pp. 38- 43 ,(2001) , 10.1038/82881
K. Han, J.L. Manley, Functional domains of the Drosophila Engrailed protein. The EMBO Journal. ,vol. 12, pp. 2723- 2733 ,(1993) , 10.1002/J.1460-2075.1993.TB05934.X
R. Grill, K. Murai, A. Blesch, F. H. Gage, M. H. Tuszynski, Cellular Delivery of Neurotrophin-3 Promotes Corticospinal Axonal Growth and Partial Functional Recovery after Spinal Cord Injury The Journal of Neuroscience. ,vol. 17, pp. 5560- 5572 ,(1997) , 10.1523/JNEUROSCI.17-14-05560.1997
Iris E. Bonilla, Katsuhisa Tanabe, Stephen M. Strittmatter, Small Proline-Rich Repeat Protein 1A Is Expressed by Axotomized Neurons and Promotes Axonal Outgrowth The Journal of Neuroscience. ,vol. 22, pp. 1303- 1315 ,(2002) , 10.1523/JNEUROSCI.22-04-01303.2002
Friedrich Laub, Rafael Aldabe, Victor Friedrich, Shunsuke Ohnishi, Teruhiko Yoshida, Francesco Ramirez, Developmental Expression of Mouse Krüppel-like Transcription Factor KLF7 Suggests a Potential Role in Neurogenesis Developmental Biology. ,vol. 233, pp. 305- 318 ,(2001) , 10.1006/DBIO.2001.0243
Jae K. Lee, Cédric G. Geoffroy, Andrea F. Chan, Kristine E. Tolentino, Michael J. Crawford, Marisa A. Leal, Brian Kang, Binhai Zheng, Assessing Spinal Axon Regeneration and Sprouting in Nogo-, MAG-, and OMgp-Deficient Mice Neuron. ,vol. 66, pp. 663- 670 ,(2010) , 10.1016/J.NEURON.2010.05.002
R. Seijffers, C. D. Mills, C. J. Woolf, ATF3 Increases the Intrinsic Growth State of DRG Neurons to Enhance Peripheral Nerve Regeneration The Journal of Neuroscience. ,vol. 27, pp. 7911- 7920 ,(2007) , 10.1523/JNEUROSCI.5313-06.2007
Ivan Sadowski, Jun Ma, Steve Triezenberg, Mark Ptashne, GAL4-VP16 is an unusually potent transcriptional activator Nature. ,vol. 335, pp. 563- 564 ,(1988) , 10.1038/335563A0
Edmund R. Hollis, Paul Lu, Armin Blesch, Mark H. Tuszynski, IGF-I gene delivery promotes corticospinal neuronal survival but not regeneration after adult CNS injury. Experimental Neurology. ,vol. 215, pp. 53- 59 ,(2009) , 10.1016/J.EXPNEUROL.2008.09.014