Rentzsch Fabian, Anton Roman, Saina Michael, Hammerschmidt Matthias, Holstein Thomas W, Technau Ulrich
Sars Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgt. 55, N-5008 Bergen, Norway.
Dev Biol. 2006 Aug 15;296(2):375-87. doi: 10.1016/j.ydbio.2006.06.003. Epub 2006 Jun 7.
The evolutionary origin of the anterior-posterior and the dorsoventral body axes of Bilateria is a long-standing question. It is unclear how the main body axis of Cnidaria, the sister group to the Bilateria, is related to the two body axes of Bilateria. The conserved antagonism between two secreted factors, BMP2/4 (Dpp in Drosophila) and its antagonist Chordin (Short gastrulation in Drosophila) is a crucial component in the establishment of the dorsoventral body axis of Bilateria and could therefore provide important insight into the evolutionary origin of bilaterian axes. Here, we cloned and characterized two BMP ligands, dpp and GDF5-like as well as two secreted antagonists, chordin and gremlin, from the basal cnidarian Nematostella vectensis. Injection experiments in zebrafish show that the ventralizing activity of NvDpp mRNA is counteracted by NvGremlin and NvChordin, suggesting that Gremlin and Chordin proteins can function as endogenous antagonists of NvDpp. Expression analysis during embryonic and larval development of Nematostella reveals asymmetric expression of all four genes along both the oral-aboral body axis and along an axis perpendicular to this one, the directive axis. Unexpectedly, NvDpp and NvChordin show complex and overlapping expression on the same side of the embryo, whereas NvGDF5-like and NvGremlin are both expressed on the opposite side. Yet, the two pairs of ligands and antagonists only partially overlap, suggesting complex gradients of BMP activity along the directive axis but also along the oral-aboral axis. We conclude that a molecular interaction between BMP-like molecules and their secreted antagonists was already employed in the common ancestor of Cnidaria and Bilateria to create axial asymmetries, but that there is no simple relationship between the oral-aboral body axis of Nematostella and one particular body axis of Bilateria.
两侧对称动物前后轴和背腹轴的进化起源是一个长期存在的问题。目前尚不清楚两侧对称动物的姐妹类群刺胞动物的主要体轴与两侧对称动物的两个体轴是如何相关的。两种分泌因子BMP2/4（果蝇中的Dpp）与其拮抗剂Chordin（果蝇中的短原肠胚形成因子）之间保守的拮抗作用是两侧对称动物背腹体轴建立的关键组成部分，因此可能为两侧对称动物体轴的进化起源提供重要见解。在这里，我们从基部刺胞动物星状海葵中克隆并鉴定了两种BMP配体dpp和GDF5样分子，以及两种分泌拮抗剂chordin和gremlin。在斑马鱼中的注射实验表明，NvGremlin和NvChordin可抵消NvDpp mRNA的腹化活性，这表明Gremlin和Chordin蛋白可作为NvDpp的内源性拮抗剂发挥作用。对星状海葵胚胎和幼虫发育过程中的表达分析揭示，所有这四个基因沿口-反口体轴以及沿与该轴垂直的轴（定向轴）均呈不对称表达。出乎意料的是，NvDpp和NvChordin在胚胎的同一侧呈现复杂且重叠的表达，而NvGDF5样分子和NvGremlin均在相反侧表达。然而，这两对配体和拮抗剂仅部分重叠，这表明BMP活性沿定向轴以及沿口-反口轴均存在复杂的梯度。我们得出结论，BMP样分子与其分泌拮抗剂之间的分子相互作用在刺胞动物和两侧对称动物的共同祖先中就已被用于产生轴向不对称，但星状海葵的口-反口体轴与两侧对称动物的某一特定体轴之间不存在简单的关系。
