Activation of Notch signaling pathway precedes heart regeneration in zebrafish
Activation of Notch signaling pathway precedes heart regeneration in zebrafish
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DOI：
10.1073/pnas.1834204100
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发表时间：
2003-09-30
影响因子：
11.1
通讯作者：
Izpisúa-Belmonte, JC
中科院分区：
文献类型：
--
作者：
Raya, A;Koth, CM;Izpisúa-Belmonte, JC
有几种脊椎动物显示出在截肢后身体部分再生的能力。在此过程中，分化的细胞重新进入细胞周期并增殖以产生大量未分化的细胞。重塑机制作用于这些细胞，最终形成再生的组织或器官，取代截肢的组织或器官。在蝾螈和斑马鱼中再生肢体/鳍的实验表明，含有同源结构域的转录因子的Msx家族的成员在芽基形成和图案化过程中发挥关键作用。在这里，我们表明，成年斑马鱼有一个显着的能力，在一个过程中，涉及msxB和msxC基因的上调心脏再生。我们目前的证据表明，心脏再生涉及一个特定的遗传程序的执行，而不是心脏发育程序的重新部署。在Msx激活之前，notch 1b和deltaC的表达显著增加，我们发现它们在鳍再生过程中也被上调。这些数据表明Notch途径在再生反应的激活中的作用。总之，我们的研究结果强调了斑马鱼作为研究再生过程和干细胞生物学的模型。这些领域的进展无疑将有助于再生医学战略的实施。
Several vertebrates display the ability to regenerate parts of their body after amputation. During this process, differentiated cells reenter the cell cycle and proliferate to generate a mass of undifferentiated cells. Repatterning mechanisms act on these cells to eventually shape a regenerated tissue or organ that replaces the amputated one. Experiments with regenerating limbs/fins in newts and zebrafish have shown that members of the Msx family of homeodomain-containing transcription factors play key roles during blastema formation and patterning. Here we show that adult zebrafish have a remarkable capacity to regenerate the heart in a process that involves up-regulation of msxB and msxC genes. We present evidence indicating that heart regeneration involves the execution of a specific genetic program, rather than redeployment of a cardiac development program. Preceding Msx activation, there is a marked increase in the expression of notch1b and deltaC, which we show are also up-regulated during fin regeneration. These data suggest a role for the Notch pathway in the activation of the regenerative response. Taken together, our results underscore the use of zebrafish as a model for investigating the process of regeneration in particular and the biology of stem cells in general. Advances in these fields will undoubtedly aid in the implementation of strategies for regenerative medicine.