Saina Michael, Genikhovich Grigory, Renfer Eduard, Technau Ulrich
Sars International Centre for Marine Molecular Biology, University of Bergen, Thormøhlensgate 55, 5008 Bergen, Norway.
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18592-7. doi: 10.1073/pnas.0900151106. Epub 2009 Oct 15.
The TGF-beta molecules Dpp/BMP2/4/7 and their antagonist Sog/Chd play a conserved role in establishing the dorso-ventral (DV) axis in bilaterians. Homologues of BMPs and the antagonist, Chordin, have been isolated from Cnidaria and show a striking asymmetric expression pattern with respect to the primary oral-aboral (OA) axis. We used Morpholino knockdowns of Nematostella dpp (bmp2/4), bmp5-8, chordin, and tolloid to investigate their function during early development of the sea anemone Nematostella vectensis. Molecular analysis of the BMP Morpholino phenotypes revealed an upregulated and radialized expression of bmps and chordin in ectoderm and endoderm indicating a negative feedback loop. Our data further suggest that BMP signaling is required for symmetry breaking of bmp and chordin expression during gastrulation. While bmps and chordin marker genes of the ectodermal OA axis extended aborally, other ectodermal markers of the OA axis were not significantly affected. By contrast, expression of other endodermal marker genes marking both the OA and the directive axis were abolished. Our data suggest that the logic of BMP2/4 signaling and the BMP antagonist, Chordin, differs significantly between Cnidaria and Bilateria, yet the double negative feedback loop detected in Nematostella bears systemic similarities with part of the regulatory network of the DV axis patterning system in amphibians.
转化生长因子-β分子Dpp/BMP2/4/7及其拮抗剂Sog/Chd在两侧对称动物背腹(DV)轴的建立中发挥着保守作用。BMPs及其拮抗剂脊索蛋白的同源物已从刺胞动物中分离出来,并显示出相对于主要口-反口(OA)轴的显著不对称表达模式。我们利用吗啉代寡核苷酸敲低海葵星状海葵dpp(bmp2/4)、bmp5-8、脊索蛋白和类 tolloid,以研究它们在星状海葵早期发育过程中的功能。对BMP吗啉代寡核苷酸表型的分子分析显示,外胚层和内胚层中bmps和脊索蛋白的表达上调并呈放射状,表明存在负反馈回路。我们的数据进一步表明,BMP信号传导是原肠胚形成过程中bmp和脊索蛋白表达对称性打破所必需的。虽然外胚层OA轴的bmps和脊索蛋白标记基因向反口方向延伸,但OA轴的其他外胚层标记物没有受到显著影响。相比之下,标记OA轴和定向轴的其他内胚层标记基因的表达被消除。我们的数据表明,刺胞动物和两侧对称动物之间,BMP2/4信号传导的逻辑和BMP拮抗剂脊索蛋白存在显著差异,但在星状海葵中检测到的双负反馈回路与两栖动物DV轴模式形成系统的部分调控网络具有系统相似性。