Establishment of Limb Regeneration System in Mouse

小鼠肢体再生系统的建立

• 批准号: 12558086
• 负责人: IDE Hiroyuki
• 金额: $ 7.74万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12558086/
• 关键词: limb; FGF; BMP; Mouse; regeneration; マウス四肢; 繊維芽細胞成長因子; FGF-10; FGFR2

Induction of limb regeneration in mouse was studied to establish limb regeneration system in higher vertebrates.Forelimbs of new-born mouse were amputated at various level, and growth factor proteins were locally applied to the amputation sites after two days.The regeneration potency changed depending on amputation level. The limbs amputated at forearm and hand level induced the hypertrophy of stump bone tissues. The limbs amputated at wrist level induced the formation of cartilage tissues at the distal margin of stump tissues.FGF-2 and FGF-4 protein applied to the amputation sites promoted the hypertrophy of bone tissues. No promotion was observed by the local application of FGF-8 and FGF-10. BMP-2 and BMP-4 induced the formation of distal structures at the amputation site.Genes of FGF receptors were applied to the amputation sites by a gene-gun. Expression of GFP injected simultaneously was observed, but no changes in cartilage pattern occurred.These results suggest the local proliferation and differentiation was induced in some FGFs and BMPs, although no stimulation was observed by FGF-10, which is known to induce limb regeneration in Xenopus laevis.

为了建立高等脊椎动物的肢体再生系统，研究了诱导小鼠肢体再生的方法。在不同程度上切除新生小鼠前肢，2天后局部应用生长因子蛋白于截肢部位。再生能力随截肢程度的不同而变化。前臂和手部水平截肢引起残肢骨组织肥大。腕部水平截肢诱导残肢远端边缘软骨组织形成。FGF-2和FGF-4蛋白应用于截肢部位促进骨组织肥厚。局部应用FGF-8和FGF-10未观察到促进作用。BMP-2和BMP-4诱导截肢部位远端结构的形成。通过基因枪将FGF受体基因应用于截肢部位。同时注射GFP观察其表达，但软骨形态未发生变化。这些结果表明，尽管FGF-10未观察到刺激作用，但某些fgf和bmp可诱导局部增殖和分化，而已知FGF-10可诱导非洲爪蟾肢体再生。

项目成果

Yokoyama, H.: "Anteroposterior axis formation in Xenopus limb bud recombinants : A model of pattern formation during limb regeneration"Developmental Dynamcs. 225. 277-288 (2002)

横山，H.：“非洲爪蟾肢芽重组体的前后轴形成：肢体再生过程中模式形成的模型”发育动力学。

D.Saito: "Specification and determination of limb identity : evidence for inhibitory regulation of Tbx gene expression"Development. 129. 211-220 (2002)

D.Saito：“肢体身份的规范和确定：Tbx 基因表达抑制调节的证据”开发。

Kimura,J. et al.: "Synergistic effects of FGF and non-ridge ectoderm on gene expression involved in the formation of the anteroposterior axis of the chick limb bud in cell culture"Development Growth & Differentiation. 42. 219-227 (2000)

木村，J.

Matsuda, H.: "An epidermal signal regulated Lmx-1 expression and dorsal-ventral pattern during Xenopus limb regeneration"Developmental Biology. 229. 351-362 (2001)

Matsuda, H.：“爪蟾肢体再生过程中表皮信号调节 Lmx-1 表达和背腹模式”发育生物学。

Saito, D.: "Specification and determination of limb identity : evidence for inhibitory regulation of Tbx gene expression"Development. 129. 211-220 (2002)

Saito, D.：“肢体身份的规范和确定：Tbx 基因表达抑制调节的证据”开发。