Impaired regenerative response of primary sensory neurons in ZPK/DLK gene-trap mice.
Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in regenerative responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
Department of Neurology, School of Medicine, University of California, Davis, 601A Shriners Hospitals for Children Northern California, Sacramento, CA 95817-2215, USA.
Aki
A
Itoh
Makoto
M
Horiuchi
Peter
P
Bannerman
David
D
Pleasure
Takayuki
T
Itoh
D000818:Animals; D001369:Axons / Q000201:enzymology / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D005727:Ganglia, Spinal / Q000166:cytology / Q000293:injuries* / Q000502:physiology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009416:Nerve Regeneration / Q000235:genetics; D011984:Sensory Receptor Cells / Q000201:enzymology / Q000502:physiology*
D048031:JNK Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C090757:mitogen-activated protein kinase kinase kinase 12