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Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract
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Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract
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Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract
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Journal Article
Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract
2012
Overview
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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Animals
/ Axons
/ cytology
/ Female
/ genetics
/ Green Fluorescent Proteins - genetics
/ Green Fluorescent Proteins - metabolism
/ Herpes Simplex Virus Protein Vmw65
/ Herpes Simplex Virus Protein Vmw65 - genetics
/ Humans
/ Kruppel-Like Transcription Factors
/ Kruppel-Like Transcription Factors - genetics
/ Kruppel-Like Transcription Factors - metabolism
/ Luminescent Measurements - methods
/ methods
/ Mice
/ Mutation
/ Nerve Regeneration - genetics
/ Nerve Regeneration - physiology
/ Neurites
/ Neurons
/ Proteins
/ Pyramidal Tracts - metabolism
/ Pyramidal Tracts - physiology
/ Rats
/ Reverse Transcriptase Polymerase Chain Reaction
/ Spinal Cord Injuries - genetics
/ Spinal Cord Injuries - metabolism
