Dataset Information

Kinesin-12 influences axonal growth during zebrafish neural development.

ABSTRACT: Kinesin-12 (also called KIF15) is a microtubule-based motor protein best known for its role in cell division. We previously reported that kinesin-12 is robustly expressed in developing terminally post-mitotic neurons, with levels diminishing as neurons reach maturity. We found that axons of cultured rodent neurons grow faster and longer if kinesin-12 is experimentally depleted, leading us to conclude that kinesin-12 plays a role in modulating axonal growth. Here we used zebrafish to explore whether these results apply to an in vivo system and whether they apply across different kinds of vertebrates. In whole mount in situ hybridization, kinesin-12 mRNA was detectable at 2-cell and 1K-cell stages. At 5.3 and 8 hours post-fertilization (hpf), hybridization signal for kinesin-12 mRNA was observed in the ectoderm. From 14 to 36 hpf, the signal had expanded to the central nervous system. At 60 hpf, the hybridization signal was concentrated in the brain. After 5 days post-fertilization, kinesin-12 expression was reduced. Kinesin-12 knockdown resulted in notably longer fast-growing axons with fewer branches by injection of a splice-blocking morpholino into Tg(huC:egfp) or Tg(hb9:gfp) zebrafish embryos. Kinesin-12 overexpression resulted in shorter axons than controls. These results are consistent with our previous observations on rodents using primary cultures for the experimental manipulations, and suggest a key role of kinesin-12 as a modulator of axonal development.

SUBMITTER: Xu M

PROVIDER: S-EPMC4236235 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Kinesin-12 influences axonal growth during zebrafish neural development.

Xu Man M Liu Dong D Dong Zhangji Z Wang Xin X Wang Xueqian X Liu Yan Y Baas Peter W PW Liu Mei M

Cytoskeleton (Hoboken, N.J.) 20141030 10

Kinesin-12 (also called KIF15) is a microtubule-based motor protein best known for its role in cell division. We previously reported that kinesin-12 is robustly expressed in developing terminally post-mitotic neurons, with levels diminishing as neurons reach maturity. We found that axons of cultured rodent neurons grow faster and longer if kinesin-12 is experimentally depleted, leading us to conclude that kinesin-12 plays a role in modulating axonal growth. Here we used zebrafish to explore whet ...[more]

PMID: 25250533

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Project description:Thyroid hormone (TH) balance is essential for vertebrate development. Deiodinase type 1 (D1) and type 2 (D2) increase and deiodinase type 3 (D3) decreases local intracellular levels of T3, the most important active TH. The role of deiodinase-mediated TH effects in early vertebrate development is only partially understood. Therefore, we investigated the role of deiodinases during early development of zebrafish until 96 hours post fertilization at the level of the transcriptome (microarray), biochemistry, morphology and physiology using morpholino (MO) knockdown. Knockdown of D1+D2 (D1D2MO) and knockdown of D3 (D3MO) both resulted in transcriptional regulation of energy metabolism and (muscle) development in abdomen and tail, together with reduced growth, impaired swim bladder inflation, reduced protein content and reduced motility. The reduced growth and impaired swim bladder inflation in D1D2MO could be due to lower levels of T3 which is known to drive growth and development. The pronounced upregulation of a large number of transcripts coding for key proteins in ATP-producing pathways in D1D2MO could reflect a compensatory response to a decreased metabolic rate, also typically linked to hypothyroidism. Compared to D1D2MO, the effects were more pronounced or more frequent in D3MO, in which hyperthyroidism is expected. More specifically, increased heart rate, delayed hatching and increased carbohydrate content were observed only in D3MO. An increase of the metabolic rate, a decrease of the metabolic efficiency and a stimulation of gluconeogenesis using amino acids as substrates may have been involved in the observed reduced protein content, growth and motility in D3MO larvae. Furthermore, expression of transcripts involved in purine metabolism coupled to vision was decreased in both knockdown conditions, suggesting that both may impair vision. This study provides new insights, not only into the role of deiodinases, but also into the importance of a correct TH balance during vertebrate embryonic development.

Dataset Information

Kinesin-12 influences axonal growth during zebrafish neural development.

Publications

Kinesin-12 influences axonal growth during zebrafish neural development.

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