Dual leucine zipper kinase is necessary for retinal ganglion cell axonal regeneration in Xenopus laevis

被引:0
|
作者
Fague, Lindsay [1 ]
Marsh-Armstrong, Nicholas [1 ]
机构
[1] Univ Calif Davis, Dept Ophthalmol & Vis Sci, UC Davis Eye Ctr, Sch Med, 75 Med Sci Drive Rm 3451, Davis, CA 95616 USA
来源
PNAS NEXUS | 2023年 / 2卷 / 05期
关键词
regeneration; Xenopus; optic nerve; retina; C-JUN EXPRESSION; TRANSCRIPTION FACTOR; MESSENGER-RNA; SCHWANN-CELLS; PROTEIN; INJURY; RESPONSES; GROWTH; DEGENERATION; MITOCHONDRIA;
D O I
10.1093/pnasnexus/pgad109
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Retinal ganglion cell (RGC) axons of the African clawed frog, Xenopus laevis, unlike those of mammals, are capable of regeneration and functional reinnervation of central brain targets following injury. Here, we describe a tadpole optic nerve crush (ONC) procedure and assessments of brain reinnervation based on live imaging of RGC-specific transgenes which, when paired with CRISPR/Cas9 injections at the one-cell stage, can be used to assess the function of regeneration-associated genes in vivo in F0 animals. Using this assay, we find that map3k12, also known as dual leucine zipper kinase (Dlk), is necessary for RGC axonal regeneration and acts in a dose-dependent manner. Loss of Dlk does not affect RGC innervation of the brain during development or visually driven behavior but does block both axonal regeneration and functional vision restoration after ONC. Dlk loss does not alter the acute changes in mitochondrial movement that occur within RGC axons hours after ONC but does completely block the phosphorylation and nuclear translocation of the transcription factor Jun within RGCs days after ONC; yet, Jun is dispensable for reinnervation. These results demonstrate that in a species fully capable of regenerating its RGC axons, Dlk is essential for the axonal injury signal to reach the nucleus but may affect regeneration through a different pathway than by which it signals in mammalian RGCs.
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页数:15
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