Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract. Proc Natl Acad Sci U S A 2012 May 08;109(19):7517-22
Date
04/25/2012Pubmed ID
22529377Pubmed Central ID
PMC3358880DOI
10.1073/pnas.1120684109Scopus ID
2-s2.0-84860828520 (requires institutional sign-in at Scopus site) 213 CitationsAbstract
Axon regeneration in the central nervous system normally fails, in part because of a developmental decline in the intrinsic ability of CNS projection neurons to extend axons. Members of the KLF family of transcription factors regulate regenerative potential in developing CNS neurons. Expression of one family member, KLF7, is down-regulated developmentally, and overexpression of KLF7 in cortical neurons in vitro promotes axonal growth. To circumvent difficulties in achieving high neuronal expression of exogenous KLF7, we created a chimera with the VP16 transactivation domain, which displayed enhanced neuronal expression compared with the native protein while maintaining transcriptional activation and growth promotion in vitro. Overexpression of VP16-KLF7 overcame the developmental loss of regenerative ability in cortical slice cultures. Adult corticospinal tract (CST) neurons failed to up-regulate KLF7 in response to axon injury, and overexpression of VP16-KLF7 in vivo promoted both sprouting and regenerative axon growth in the CST of adult mice. These findings identify a unique means of promoting CST axon regeneration in vivo by reengineering a developmentally down-regulated, growth-promoting transcription factor.
Author List
Blackmore MG, Wang Z, Lerch JK, Motti D, Zhang YP, Shields CB, Lee JK, Goldberg JL, Lemmon VP, Bixby JLAuthor
Murray Blackmore PhD Assistant Professor in the School of Allied Health department at Marquette UniversityMESH terms used to index this publication - Major topics in bold
AnimalsAxons
Cells, Cultured
Etoposide
Female
Gene Expression
Genetic Engineering
Green Fluorescent Proteins
HEK293 Cells
Herpes Simplex Virus Protein Vmw65
Humans
Immunohistochemistry
Kruppel-Like Transcription Factors
Luminescent Measurements
Mice
Mice, Inbred C57BL
Mutation
Nerve Regeneration
Neurites
Neurons
Pyramidal Tracts
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord Injuries
Transcriptional Activation
