A role of Yamanaka's factor during fish optic nerve regeneration after nerve injury

山中因子在神经损伤后鱼视神经再生中的作用

• 批准号: 23650163
• 负责人: KATO Satoru
• 金额: $ 2.33万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23650163/
• 关键词: 魚; 視神経再生; sox2; klf4; c-myc; oct3/4; 神経幹細胞; 神経損傷; 山中因子; ネスチン; LIF; ゼブラフィッシュ; 網膜神経節細胞; ｋｌｆ4

Unlike mammals, fish optic nerve can regenerate after nerve injury. We have a hypothesis of this regenerative capacity of fish optic nerve that mature retinal ganglion cells (RGCs) in fish are reprogrammed to neural stem-cell like cells by optic nerve injury. To certain this hypothesis, we investigated expression levels of sox2, klf4, c-myc and nestin in the zebrafish retina after optic nerve injury. The levels of sox2, klf4 and c-myc mRNA increased in the retina 3 days after axotomy. The level of a neural stem cell marker, nestin increased in the retina 4-5 days after axotomy. These molecules were all localized to the RGCs. Furthermore, we found that leukemia inhibitory factor (LIF) was positional as an upstream signal to the klf4 and sox2. In the presence of LIF in culture medium of retinal explant, a significant neurite outgrowth could be seen as compared to the no treatment, control. In contrast, the inhibition of LIF signals leaded to the suppression of neurite outgrowth from retina. Therefore, we conclude that the capability of fish optic nerve regeneration is due to reprograming mechanism of matured RGCs after optic nerve injury.

与哺乳动物不同，鱼视神经可以在神经损伤后再生。我们对鱼视神经的这种再生能力有一个假设，即鱼中成熟的视网膜神经节细胞（RGC）通过视神经损伤将鱼类的成熟视网膜神经节细胞（RGC）重编程为神经干细胞。为了确定这一假设，我们研究了视神经损伤后斑马鱼视网膜中SOX2，KLF4，C-MYC和NESTIN的表达水平。轴突切开后3天，视网膜中SOX2，KLF4和C-MYC mRNA的水平升高。轴突切开术后4-5天，Nestin的神经干细胞标记水平升高。这些分子都位于RGC中。此外，我们发现白血病抑制因子（LIF）是KLF4和SOX2的上游信号。在视网膜外植体培养基中存在LIF的情况下，与无治疗，对照相比，可以看到明显的神经突生长。相反，对LIF信号的抑制导致了视网膜神经突生长的抑制。因此，我们得出的结论是，鱼视神经再生的能力是由于视神经损伤后的成熟RGC的重编程机制所致。

项目成果

A distinct effect of two types of transglutaminase on fish optic nerve regeneration

两种转谷氨酰胺酶对鱼类视神经再生的不同作用

• 发表时间: 2012
• 作者: Furumoto T;Fujita K;Toyoshima M;Zaiki K;Sahara S;Akita M;Ozawa N;Nakaoji K;Hamada K;Tamai K;Kaneda Y;Maeda A.;杉 谷 加 代
• 通讯作者: 杉 谷 加 代

ゼブラフィッシュ視神経損傷後に発現する再生関連因子としてのNeuroglobinについて

神经球蛋白作为斑马鱼视神经损伤后表达的再生相关因子

• 发表时间: 2013
• 作者: 杉谷加代;大貝和裕;若杉桂輔;加藤 聖
• 通讯作者: 加藤 聖

Regeneration-associated genes on optic nerve regeneration in fish retina

鱼类视网膜视神经再生的再生相关基因

• 发表时间: 2013
• 期刊: Adv. Exp. Med. Biol.
• 作者: Mochida;S;Ogai K
• 通讯作者: Ogai K

Regeneration-associated genes in the zebrafish retina during optic nerve regeneration.

视神经再生过程中斑马鱼视网膜中的再生相关基因。

• 发表时间: 2011
• 作者: Sasaki T;Nakamura K;Sasada K;Okada S;Cheng XW;Suzuki T;Murohara T;Sato K;Kuzuya M.;Maki Nishitani
• 通讯作者: Maki Nishitani

Yamanaka factors expressions in the zebrafish retina during optic nerve regeneration.

山中伸弥在视神经再生过程中影响斑马鱼视网膜的表达。

• 发表时间: 2011
• 作者: Tanaka YR;Tanaka YH;Konno M,Fujiyama F;Sonomura T;Okamoto-FurutaK;Kameda H;Hioki H;Furuta T,Nakamura KC;Kaneko T;Yasunori Hayashi;Maki Nishitani
• 通讯作者: Maki Nishitani