School of Natural Sciences and Martin Ryan Marine Science Institute, National University of Ireland Galway, Galway, Ireland.
PLoS One. 2011 Apr 28;6(4):e19443. doi: 10.1371/journal.pone.0019443.
COUP transcription factors are required for the regulation of gene expression underlying development, differentiation, and homeostasis. They have an evolutionarily conserved function, being a known marker for neurogenesis from cnidarians to vertebrates. A homologue of this gene was shown previously to be a neuronal and nematocyte differentiation marker in Hydra. However, COUP-TFs had not previously been studied in a colonial cnidarian.
METHODOLOGY/PRINCIPAL FINDINGS: We cloned a COUP-TF homologue from the colonial marine cnidarian Hydractinia echinata. Expression of the gene was analysed during normal development, allorecognition events and ectopic Wnt activation, using in situ hybridisation and quantitative PCR. During normal Hydractinia development, the gene was first expressed in post-gastrula stages. It was undetectable in larvae, and its mRNA was present again in putative differentiating neurons and nematocytes in post-metamorphic stages. Global activation of canonical Wnt signalling in adult animals resulted in the upregulation of COUP-TF. We also monitored a strong COUP-TF upregulation in stolons undergoing allogeneic interactions. COUP-TF mRNA was most concentrated in the tissues that contacted allogeneic, non-self tissues, and decreased in a gradient away from the contact area. Interestingly, the gene was transiently upregulated during initial contact of self stolons, but dissipated rapidly following self recognition, while in non-self contacts high expression levels were maintained.
CONCLUSIONS/SIGNIFICANCE: We conclude that COUP-TF is likely involved in neuronal/nematocyte differentiation in a variety of contexts. This has now been shown to include allorecognition, where COUP-TF is thought to have been co-opted to mediate allorejection by recruiting stinging cells that are the effectors of cytotoxic rejection of allogeneic tissue. Our findings that Wnt activation upregulates COUP-TF expression suggests that Wnts' role in neuronal differentiation could be mediated through COUP-TF.
COUP 转录因子对于从刺胞动物到脊椎动物的神经发生的基因表达调控是必需的。它们具有进化上保守的功能，是神经发生的已知标记物。先前的研究表明，该基因的同源物是水螅中的神经元和刺细胞分化标记物。然而，COUP-TF 以前并未在群体刺胞动物中进行过研究。
方法/主要发现：我们从群体海洋刺胞动物 Hydractinia echinata 中克隆了一个 COUP-TF 同源物。使用原位杂交和定量 PCR 分析了该基因在正常发育、异体识别事件和异位 Wnt 激活过程中的表达。在正常的 Hydractinia 发育过程中，该基因首先在原肠胚后阶段表达。在幼虫中无法检测到，在变态后的阶段，其 mRNA 再次存在于推测的分化神经元和刺细胞中。在成年动物中，经典 Wnt 信号的全局激活导致 COUP-TF 的上调。我们还监测到在进行同种异体相互作用的茎中 COUP-TF 的强烈上调。COUP-TF mRNA 主要集中在与异体、非自身组织接触的组织中，并从接触区域逐渐减少。有趣的是，该基因在自身茎的初始接触期间短暂上调，但在自我识别后迅速消散，而在非自我接触中保持高表达水平。
结论/意义：我们得出结论，COUP-TF 可能在各种情况下参与神经元/刺细胞分化。这已经表明包括异体识别，在异体识别中，COUP-TF 被认为通过招募是同种异体组织细胞毒性排斥的效应物刺细胞来介导异体排斥。我们发现 Wnt 激活上调 COUP-TF 表达表明 Wnt 在神经元分化中的作用可能是通过 COUP-TF 介导的。
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