scholarly journals Gene expression analysis of zebrafish retinal ganglion cells during optic nerve regeneration identifies KLF6a and KLF7a as important regulators of axon regeneration

2007 ◽  
Vol 312 (2) ◽  
pp. 596-612 ◽  
Author(s):  
Matthew B. Veldman ◽  
Michael A. Bemben ◽  
Robert C. Thompson ◽  
Daniel Goldman
2019 ◽  
Author(s):  
Xue-Wei Wang ◽  
Shu-Guang Yang ◽  
Chi Zhang ◽  
Jin-Jin Ma ◽  
Yingchi Zhang ◽  
...  

AbstractIn addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here we showed that knocking out myosin IIA/B in retinal ganglion cells alone either before or after optic nerve crush induced marked and sustained optic nerve regeneration. Combined Lin28 overexpression and myosin IIA/B knockout led to synergistic promoting effect and long-distance axon regeneration. Immunostaining, RNA-seq and western blot analyses revealed that myosin II deletion did not affect known axon regeneration signaling pathways or the expression of regeneration associated genes. Instead, it abolished the retraction bulb formation and significantly enhanced the axon extension efficiency. The study provided clear evidence that directly targeting neuronal cytoskeleton was sufficient to induce strong CNS axon regeneration, and combining gene expression in the soma and modified cytoskeletal dynamics in the axon was a promising approach for long-distance CNS axon regeneration.


Cell Reports ◽  
2020 ◽  
Vol 31 (3) ◽  
pp. 107537 ◽  
Author(s):  
Xue-Wei Wang ◽  
Shu-Guang Yang ◽  
Chi Zhang ◽  
Ming-Wen Hu ◽  
Jiang Qian ◽  
...  

2007 ◽  
Vol 50 (5) ◽  
pp. 749-756 ◽  
Author(s):  
Yoshiki Koriyama ◽  
Keiko Homma ◽  
Kayo Sugitani ◽  
Yoshihiro Higuchi ◽  
Toru Matsukawa ◽  
...  

2008 ◽  
Vol 28 (2) ◽  
pp. 548-561 ◽  
Author(s):  
I. Soto ◽  
E. Oglesby ◽  
B. P. Buckingham ◽  
J. L. Son ◽  
E. D. O. Roberson ◽  
...  

2021 ◽  
Vol 118 (9) ◽  
pp. e2017282118 ◽  
Author(s):  
Lili Xie ◽  
Yuqin Yin ◽  
Larry Benowitz

Ciliary neurotrophic factor (CNTF) is a leading therapeutic candidate for several ocular diseases and induces optic nerve regeneration in animal models. Paradoxically, however, although CNTF gene therapy promotes extensive regeneration, recombinant CNTF (rCNTF) has little effect. Because intraocular viral vectors induce inflammation, and because CNTF is an immune modulator, we investigated whether CNTF gene therapy acts indirectly through other immune mediators. The beneficial effects of CNTF gene therapy remained unchanged after deleting CNTF receptor alpha (CNTFRα) in retinal ganglion cells (RGCs), the projection neurons of the retina, but were diminished by depleting neutrophils or by genetically suppressing monocyte infiltration. CNTF gene therapy increased expression of C-C motif chemokine ligand 5 (CCL5) in immune cells and retinal glia, and recombinant CCL5 induced extensive axon regeneration. Conversely, CRISPR-mediated knockdown of the cognate receptor (CCR5) in RGCs or treating wild-type mice with a CCR5 antagonist repressed the effects of CNTF gene therapy. Thus, CCL5 is a previously unrecognized, potent activator of optic nerve regeneration and mediates many of the effects of CNTF gene therapy.


1981 ◽  
Vol 89 (1) ◽  
pp. 86-95 ◽  
Author(s):  
J H Skene ◽  
M Willard

In an effort to understand the regulation of the transition of a mature neuron to the growth, or regenerating, state we have analyzed the composition of the axonally transported proteins in the retinal ganglion cells of the toad Bufo marinus after inducing axon regeneration by crushing the optic nerve. At increasing intervals after axotomy, we labeled the retinal ganglion cells with [35S]methionine and subsequently analyzed the labeled transported polypeptides in the crushed optic nerve by means of one- and two-dimensional electrophoretic techniques. The most significant conclusion from these experiments is that, while the transition from the mature to the regenerating state does not require a gross qualitative alteration in the composition of axonally transported proteins, the relative labeling of a small subset of rapidly transported proteins is altered dramatically (changes of more than 20-fold) and reproducibly (more than 30 animals) by axotomy. One of these growth-associated proteins (GAPs) was soluble in an aqueous buffer, while three were associated with a crude membrane fraction. The labeling of all three of the membrane-associated GAPs increased during the first 8 d after axotomy, and they continued to be labeled for at least 4 wk. The modulation of these proteins after axotomy is consistent with the possibility that they are involve in growth-specific functions and that the altered expression of a small number of genes is a crucial regulatory event in the transition of a mature neuron to a growth state. In addition to these selective changes in rapidly transported proteins, we observed the following more general metabolic correlates of the regeneration process: The total radioactive label associated with the most rapidly transported proteins (groups I and II) increased three to fourfold during the first 8 d after the nerve was crushed, while the total label associated with more slowly moving proteins (group IV) increased about 10-fold during this same period. Among these more slowly transported polypeptides, five were observed whose labeling increased much more than the average. Three of these five polypeptides resemble actin and alpha- and beta-tubulin in their electrophoretic properties.


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