Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.
Tracing notochord-derived cells using a Noto-cre mouse: implications for intervertebral disc development.
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使用 Noto-cre 小鼠追踪脊索衍生细胞：对椎间盘发育的影响。
DOI：
10.1242/dmm.008128
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发表时间：
2012-01
影响因子：
4.3
通讯作者：
Séguin CA
中科院分区：
文献类型：
--
作者：
McCann MR;Tamplin OJ;Rossant J;Séguin CA
与椎间盘退变相关的背痛是最常见的肌肉骨骼问题，终生患病率为82%。缺乏有效的治疗方法，这一广泛的问题是直接关系到我们有限的了解椎间盘的发展，维护和退化。本研究的目的是使用一种新的脊索特异性Cre小鼠来确定椎间盘内髓核细胞的发育起源。为了追踪椎间盘内脊索细胞的命运，我们通过靶向同源框基因诺托获得了脊索特异性Cre小鼠系。在原肠胚形成期间[胚胎7.5天（E7.5）-E12.5]，该基因的表达仅限于结和后脊索。将Noto-cre小鼠与条件lacZ报告基因杂交，以观察整装胚胎中脊索的命运。我们进行了谱系追踪实验，以检查从E12.5到脊椎成熟小鼠（9个月）脊索对脊髓发育的贡献。命运定位研究表明，在原始中轴骨骼伸长和形成之后，脊索在完全形成的椎间盘中产生髓核。β-半乳糖苷酶（由lacZ编码）和细胞角蛋白-8的细胞定位表明，脊索细胞和软骨细胞样髓核细胞均来源于胚胎脊索。这些研究最终确定脊索细胞是成熟椎间盘髓核内所有细胞的胚胎前体。这表明脊索细胞可能作为椎间盘内的组织特异性祖细胞，并建立了Noto-cre小鼠作为一种独特的工具，询问脊索细胞对椎间盘发育和椎间盘退变的贡献。
Back pain related to intervertebral disc degeneration is the most common musculoskeletal problem, with a lifetime prevalence of 82%. The lack of effective treatment for this widespread problem is directly related to our limited understanding of disc development, maintenance and degeneration. The aim of this study was to determine the developmental origins of nucleus pulposus cells within the intervertebral disc using a novel notochord-specific Cre mouse. To trace the fate of notochordal cells within the intervertebral disc, we derived a notochord-specific Cre mouse line by targeting the homeobox gene Noto. Expression of this gene is restricted to the node and the posterior notochord during gastrulation [embryonic day 7.5 (E7.5)-E12.5]. The Noto-cre mice were crossed with a conditional lacZ reporter for visualization of notochord fate in whole-mount embryos. We performed lineage-tracing experiments to examine the contribution of the notochord to spinal development from E12.5 through to skeletally mature mice (9 months). Fate mapping studies demonstrated that, following elongation and formation of the primitive axial skeleton, the notochord gives rise to the nucleus pulposus in fully formed intervertebral discs. Cellular localization of β-galactosidase (encoded by lacZ) and cytokeratin-8 demonstrated that both notochordal cells and chondrocyte-like nucleus pulposus cells are derived from the embryonic notochord. These studies establish conclusively that notochordal cells act as embryonic precursors to all cells found within the nucleus pulposus of the mature intervertebral disc. This suggests that notochordal cells might serve as tissue-specific progenitor cells within the disc and establishes the Noto-cre mouse as a unique tool to interrogate the contribution of notochordal cells to both intervertebral disc development and disc degeneration.
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影响因子：
2.5
作者：
Choi, Kyung-Suk;Cohn, Martin J.;Harfe, Brian D.
通讯作者：
Harfe, Brian D.
影响因子：
3
作者：
Kim, KW;Lim, TH;An, HS
通讯作者：
An, HS
影响因子：
3
作者：
Kawaguchi, Y;Osada, R;Kimura, T
通讯作者：
Kimura, T
DOI：
10.1073/pnas.0912818107
发表时间：
2010-03-23
影响因子：
11.1
作者：
Bouldin, Cortney M.;Gritli-Linde, Amel;Harfe, Brian D.
通讯作者：
Harfe, Brian D.
影响因子：
3
作者：
Liebscher, Thomas;Haefeli, Mathias;Boos, Norbert
通讯作者：
Boos, Norbert