Raya Angel, Koth Christopher M, Büscher Dirk, Kawakami Yasuhiko, Itoh Tohru, Raya R Marina, Sternik Gabriel, Tsai Huai-Jen, Rodríguez-Esteban Concepción, Izpisúa-Belmonte Juan Carlos
Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1(Suppl 1):11889-95. doi: 10.1073/pnas.1834204100. Epub 2003 Aug 8.
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.
几种脊椎动物在截肢后显示出身体部分再生的能力。在此过程中，分化细胞重新进入细胞周期并增殖，以产生大量未分化细胞。重新模式化机制作用于这些细胞，最终形成一个再生组织或器官来替代被截肢的部分。对蝾螈和斑马鱼的再生肢体/鳍进行的实验表明，含同源结构域的转录因子Msx家族成员在芽基形成和模式化过程中起关键作用。在这里，我们表明成年斑马鱼在一个涉及msxB和msxC基因上调的过程中具有显著的心脏再生能力。我们提供的证据表明，心脏再生涉及执行特定的遗传程序，而不是重新部署心脏发育程序。在Msx激活之前，notch1b和deltaC的表达显著增加，我们发现在鳍再生过程中它们也会上调。这些数据表明Notch信号通路在激活再生反应中起作用。综上所述，我们的结果强调了斑马鱼作为一个模型，尤其可用于研究再生过程以及一般意义上的干细胞生物学。这些领域的进展无疑将有助于实施再生医学策略。
