Fgf and Sdf-1 Pathways Interact during Zebrafish Fin Regeneration
Fgf and Sdf-1 Pathways Interact during Zebrafish Fin Regeneration
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DOI：
10.1371/journal.pone.0005824
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发表时间：
2009-06-08
期刊：
影响因子：
3.7
通讯作者：
Vriz, Sophie
中科院分区：
文献类型：
--
作者：
Bouzaffour, Mohamed;Dufourcq, Pascale;Vriz, Sophie
趋化因子基质细胞衍生因子-1（SDF 1）最初被鉴定为前B细胞刺激因子，但最近已涉及分化和形态发生的其他几个关键步骤。此外，SDF 1以及FGF信号通路最近已被证明参与控制表型再生。在这份报告中，我们解决的问题，在成年斑马鱼鳍再生的两个信号通路之间可能的相互作用。使用药物和遗传工具的组合，我们表明，在epimorphic再生，sdf 1的表达，以及其同源受体，cxcr 4a，cxcr 4 b和cxcr 7的FGF信号控制。我们进一步表明，Sdf 1a负调控fgf 20 a的表达。总之，这些结果使我们提出：1）Fgf在芽基形成中的功能至少部分地由趋化因子Sdf 1a中继，并且2）Sdf 1对Fgf通路施加负反馈，这有助于在再生开始时Fgf 20 a下游基因的瞬时表达。然而，这种反馈控制可以被绕过，因为Sdf 1无效突变体再生它们的鳍，尽管较慢。到目前为止，很少分离出再生过程的突变体，这说明了鉴定再生所必需的基因的困难。这一观察结果支持了再生过程涉及多个途径之间微妙平衡的观点。
The chemokine stromal cell-derived factor-1 (SDF1) was originally identified as a pre-B cell stimulatory factor but has been recently implicated in several other key steps in differentiation and morphogenesis. In addition, SDF1 as well as FGF signalling pathways have recently been shown to be involved in the control of epimorphic regeneration. In this report, we address the question of a possible interaction between the two signalling pathways during adult fin regeneration in zebrafish. Using a combination of pharmaceutical and genetic tools, we show that during epimorphic regeneration, expression of sdf1, as well as of its cognate receptors, cxcr4a, cxcr4b and cxcr7 are controlled by FGF signalling. We further show that, Sdf1a negatively regulates the expression of fgf20a. Together, these results lead us to propose that: 1) the function of Fgf in blastema formation is, at least in part, relayed by the chemokine Sdf1a, and that 2) Sdf1 exerts negative feedback on the Fgf pathway, which contributes to a transient expression of Fgf20a downstream genes at the beginning of regeneration. However this feedback control can be bypassed since the Sdf1 null mutants regenerate their fin, though slower. Very few mutants for the regeneration process were isolated so far, illustrating the difficulty in identifying genes that are indispensable for regeneration. This observation supports the idea that the regeneration process involves a delicate balance between multiple pathways.