Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine
Bone patterning is altered in the regenerating zebrafish caudal fin after ectopic expression of sonic hedgehog and bmp2b or exposure to cyclopamine
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DOI：
10.1073/pnas.122571799
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发表时间：
2002-06-25
影响因子：
11.1
通讯作者：
Akimenko, MA
中科院分区：
文献类型：
--
作者：
Quint, E;Smith, A;Akimenko, MA
截除斑马鱼尾鳍刺激真皮骨骼再生及声音刺猬（shh）信号通路基因的再表达。表达模式表明shh信号在真皮骨再生的分泌和模式中的作用，但直接作用尚未得到证实。我们建立了一种体内基因转染的方法，在再生鳍的芽基中表达异位基因。胚泡诱导的过量骨沉积和再生骨模式改变中shh或bmp 2的异位表达。骨形态发生蛋白（bmp）信号抑制剂chordin的异位表达可拮抗shh异位表达的作用。我们通过暴露于环巴胺破坏了再生鳍中的shh信号，并发现了鳍生长的剂量依赖性抑制，每个鳍条远端区域黑素细胞的积累，放线菌的损失，以及间充质细胞增殖的减少。形态学的变化伴随着一个扩大，然后减少，在shh表达和ptc 1表达的快速废除域。这些结果暗示shh和bmp 2b信号传导参与芽基中专门的骨分泌细胞的增殖和/或分化，并表明shh表达可能受到调节反馈机制的控制，该机制定义了长出的鳍中的骨分泌区域。
Amputation of the zebrafish caudal fin stimulates regeneration of the dermal skeleton and reexpression of sonic hedgehog (shh)-signaling pathway genes. Expression patterns suggest a role for shh signaling in the secretion and patterning of the regenerating dermal bone, but a direct role has not been demonstrated. We established an in vivo method of gene transfection to express ectopically genes in the blastema of regenerating fins. Ectopic expression of shh or bmp2 in the blastema-induced excess bone deposition and altered patterning of the regenerate. The effects of shh ectopic expression could be antagonized by ectopic expression of chordin, an inhibitor of bone morphogenetic protein (bmp) signaling. We disrupted shh signaling in the regenerating fin by exposure to cyclopamine and found a dose-dependent inhibition of fin outgrowth, accumulation of melanocytes in the distal region of each fin ray, loss of actinotrichia, and reduction in cell proliferation in the mesenchyme. Morphological changes were accompanied by an expansion, followed by a reduction, in domains of shh expression and a rapid abolition of ptc1 expression. These results implicate shh and bmp2b signaling in the proliferation and/or differentiation of specialized bone-secreting cells in the blastema and suggest shh expression may be controlled by regulatory feedback mechanisms that define the region of bone secretion in the outgrowing fin.