九头蛇具有不限于单个器官但涵盖整个身体的再生能力。各种全球和综合基因组,转录组和蛋白质组方法表明,脊椎动物中存在的许多信号通路和转录因子已经存在于Cnidaria中,Bilateria的姐妹团体,并且在再生中也被激活。现在有可能研究再生生物学的核心问题之一,即,图案化系统如何被启动再生的损伤信号激活。这篇综述将介绍在Hydra中获得的当前数据,并与Bilateria的再生相似。该全局分析的重要发现是Wnt信号通路在再生过程中具有双重功能。在早期阶段,Wnt通常被激活,而在图案形成的第二阶段,其以位置特异性方式被激活。因此,Wnt信号是一般损伤反应的一部分,其中丝裂原激活的蛋白激酶(MAPK)最初通过钙和活性氧(ROS)激活。MAPKs,p38,c-JunN末端激酶(JNKs)和细胞外信号调节激酶(ERK)对于九头蛇和足再生中的Wnt激活至关重要。此外,ERK信号通路和应激诱导的MAPK之间的拮抗作用导致细胞凋亡和有丝分裂的平衡诱导。然而,早期的Wnt基因被MAPK信号而不是凋亡激活。早期Wnt基因活性与稳定的差异整合,沿主体轴的基于β-Catenin的梯度保持轴向极性并激活再生头中的进一步Wnts。因为MAPK和Wnt在进化上是高度保守的,我们假设这种机制也存在于脊椎动物中,但可能在早期Wnt基因整合水平上被不同程度地激活。
Hydra has a regenerative capacity that is not limited to individual organs but encompasses the entire body. Various global and integrative genome, transcriptome and proteome approaches have shown that many of the signaling pathways and transcription factors present in vertebrates are already present in Cnidaria, the sister group of Bilateria, and are also activated in regeneration. It is now possible to investigate one of the central questions of regeneration biology, i.e., how does the patterning system become activated by the injury signals that initiate regeneration. This review will present the current data obtained in Hydra and draw parallels with regeneration in Bilateria. Important findings of this global analysis are that the Wnt signaling pathway has a dual function in the regeneration process. In the early phase Wnt is activated generically and in a second phase of pattern formation it is activated in a position specific manner. Thus, Wnt signaling is part of the generic injury response, in which mitogen-activated protein kinases (MAPKs) are initially activated via calcium and reactive oxygen species (ROS). The MAPKs, p38, c-Jun N-terminal kinases (JNKs) and extracellular signal-regulated kinases (ERK) are essential for Wnt activation in Hydra head and foot regenerates. Furthermore, the antagonism between the ERK signaling pathway and stress-induced MAPKs results in a balanced induction of apoptosis and mitosis. However, the early Wnt genes are activated by MAPK signaling rather than apoptosis. Early Wnt gene activity is differentially integrated with a stable, β-Catenin-based gradient along the primary body axis maintaining axial polarity and activating further Wnts in the regenerating head. Because MAPKs and Wnts are highly evolutionarily conserved, we hypothesize that this mechanism is also present in vertebrates but may be activated to different degrees at the level of early Wnt gene integration.