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Journal article
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated kif15 mutations accelerate axonal outgrowth during neuronal development and regeneration in zebrafish
Traffic (Copenhagen, Denmark), v 20(1), pp 71-81
Jan 2019
PMID: 30411440
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
KIF15, the vertebrate kinesin-12, is best known as a mitotic motor protein, but continues to be expressed in neurons. Like KIF11 (the vertebrate kinesin-5), KIF15 interacts with microtubules in the axon to limit their sliding relative to one another. Unlike KIF11, KIF15 also regulates interactions between microtubules and actin filaments at sites of axonal branch formation and in growth cones. Our original work on these motors was done on cultured rat neurons, but we are now using zebrafish to extend these studies to an in vivo model. We previously studied kif15 in zebrafish by injecting splice-blocking morpholinos injected into embryos. Consistent with the cell culture work, these studies demonstrated that axons grow faster and longer when KIF15 levels are reduced. In the present study, we applied CRISPR/Cas9-based knockout technology to create kif15 mutants and labeled neurons with Tg(mnx1:GFP) transgene or transient expression of elavl3:EGFP-alpha tubulin. We then compared by live imaging the homozygotic, heterozygotic mutants to their wildtype siblings to ascertain the effects of depletion of kif15 during Caudal primary motor neuron and Rohon-Beard (R-B) sensory neuron development. The results showed, compared to the kif15 wildtype, the number of branches was reduced while axon outgrowth was accelerated in kif15 homozygotic and heterozygotic mutants. In R-B sensory neurons, after laser irradiation, injured axons with loss of kif15 displayed significantly greater regenerative velocity. Given these results and the fact that kif15 drugs are currently under development, we posit kif15 as a novel target for therapeutically augmenting regeneration of injured axons.
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Details
- Title
- Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9-mediated kif15 mutations accelerate axonal outgrowth during neuronal development and regeneration in zebrafish
- Creators
- Zhangji Dong - Nantong UniversityShuwen Wu - Nantong UniversityChenwen Zhu - Nantong UniversityXueting Wang - Nantong UniversityYuanyuan Li - Nantong UniversityXu Chen - Nantong UniversityDong Liu - Nantong UniversityLiang Qiang - Drexel UniversityPeter W Baas - Drexel UniversityMei Liu - Nantong University
- Publication Details
- Traffic (Copenhagen, Denmark), v 20(1), pp 71-81
- Publisher
- Wiley
- Grant note
- R01 NS028785 / NINDS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000453372000005
- Scopus ID
- 2-s2.0-85057895791
- Other Identifier
- 991019168156004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology