Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration
Simplet controls cell proliferation and gene transcription during zebrafish caudal fin regeneration
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DOI：
10.1016/j.ydbio.2008.09.032
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发表时间：
2009-01-15
影响因子：
2.7
通讯作者：
Antos, Christopher L.
中科院分区：
文献类型：
--
作者：
Kizil, Caghan;Otto, Georg W.;Antos, Christopher L.
脊椎动物表型再生的两个标志是正常静止细胞增殖的显著增加和在胚胎发育期间活跃的基因的重新激活。目前还不清楚是什么分子决定因素调节这些事件，以及它们是如何协调的。斑马鱼具有通过调节细胞增殖和基因转录来再生多种复合结构的能力。我们报告fam 53 b/simplet（smp）调节细胞增殖和特定基因的转录。原位杂交和定量RT-PCR实验表明，切断斑马鱼的心脏和鳍导致smp基因的强烈上调。在再生的成鳍中，smp在远端间充质中的表达仍然很强，随后扩展到远端表皮和远端尖端上皮的基底层。通过BrdU掺入和组蛋白H3磷酸化测量，吗啉敲低SMP通过降低细胞增殖来降低再生产物。此外，snip基因敲除增加了msxb，msxc和shh的表达，以及后来异位骨的形成。总之，这些数据表明，通过控制细胞增殖，特定基因的调节和适当的骨模式，在鳍再生条的要求。(C)2008年爱思唯尔公司All rights reserved.
Two hallmarks of vertebrate epimorphic regeneration are a significant increase in the proliferation of normally quiescent cells and a re-activation of genes that are active during embryonic development. It is unclear what the molecular determinants are that regulate these events and how they are coordinated. Zebrafish have the ability to regenerate several compound structures by regulating cell proliferation and gene transcription. We report that fam53b/simplet (smp) regulates both cell proliferation and the transcription of specific genes. in situ hybridization and quantitative RT-PCR experiments showed that amputation of zebrafish hearts and fins resulted in strong up-regulation of the smp gene. In regenerating adult fin, smp expression remained strong in the distal mesenchyme which later expanded to the basal layers of the distal epidermis and distal tip epithelium. Morpholino knockdown of smp reduced regenerative outgrowth by decreasing cell proliferation as measured by BrdU incorporation and histone H3 phosphorylation. In addition, snip knockdown increased the expression of msxb, msxc, and shh, as well as the later formation of ectopic bone. Taken together, these data indicate a requirement for strip in fin regeneration through control of cell proliferation, the regulation of specific genes and proper bone patterning. (C) 2008 Elsevier Inc. All rights reserved.