KLF family members regulate intrinsic axon regeneration ability.
Neurons in the central nervous system (CNS) lose their ability to regenerate early in development, but the underlying mechanisms are unknown. By screening genes developmentally regulated in retinal ganglion cells (RGCs), we identified Krüppel-like factor-4 (KLF4) as a transcriptional repressor of axon growth in RGCs and other CNS neurons. RGCs lacking KLF4 showed increased axon growth both in vitro and after optic nerve injury in vivo. Related KLF family members suppressed or enhanced axon growth to differing extents, and several growth-suppressive KLFs were up-regulated postnatally, whereas growth-enhancing KLFs were down-regulated. Thus, coordinated activities of different KLFs regulate the regenerative capacity of CNS neurons.
Moore
Darcie L
DL
Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Blackmore
Murray G
MG
Hu
Ying
Y
Kaestner
Klaus H
KH
Bixby
John L
JL
Lemmon
Vance P
VP
Goldberg
Jeffrey L
JL
D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D015536:Down-Regulation; D055786:Gene Knockout Techniques; D020439:Growth Cones / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009409:Nerve Crush; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D020221:Optic Nerve Injuries / Q000503:physiopathology; D051381:Rats; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
C000715468:Klf4 protein, mouse; C000715469:Klf4 protein, rat; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors