class="head no_bottom_margin" id="sec1title">IntroductionBone morphogenetic protein (BMP) signaling regulates dorso-ventral (DV) axis patterning in Bilateria. Binding of a homo- or heterodimeric BMP ligand to the BMP receptor leads to phosphorylation of SMAD1/5/8, which enters the nucleus together with SMAD4 and regulates transcription of target genes (). Several BMP family molecules, BMP2/4, BMP5-8, ADMP, and Gdf5/6, use this pathway, however, the most prominent members of the family are BMP2/4 and BMP5-8. Signaling is regulated extracellularly by several antagonists, including Chordin, which binds to BMPs and prevents them from binding their receptors (). In contrast to other BMP antagonists, Chordin can be cleaved by Tolloid metalloprotease, resulting in the release of active BMP ligand (). Thus, Chordin acts as a BMP shuttle diffusing away from Chordin source and promoting signaling at a distance ().These interactions form a BMP signaling gradient patterning the DV axis in vertebrates and insects, leading to the idea of a common evolutionary origin of the DV axis in Bilateria (). Indeed, in vertebrates and in Drosophila, bmp4 and chordin homologs are expressed at the opposite ends of the DV axis (A), and the position of the CNS is defined by suppression of BMP signaling, independent of whether the CNS is dorsal, as in vertebrates, or ventral, as in flies. Yet, even within Bilateria, variations regarding expression domains and network topology exist. For example, sea urchin bmp4 and chordin are co-expressed on the same side of the DV axis (A; ), and many molecules were shown to play crucial roles in DV patterning in some phyla but not in others (), which raises the question of the ancestral condition in Bilateria. In this respect Cnidaria, the sister group to Bilateria (), is pivotal for understanding the evolution of key bilaterian traits. Among cnidarians, Anthozoa (corals, sea anemones) encompass bilaterally symmetric animals with a directive axis orthogonal to the oral-aboral axis. Previous work demonstrated that the directive axis of the sea anemone Nematostella vectensis is marked by asymmetric expression of BMPs and BMP antagonists (), pointing at the possible common evolutionary origin of the directive axis and the bilaterian DV axis.BMP Signaling Is Strongest on GDF5-like-Expressing Side of Nematostella Embryo(A) Positions of chordin (blue) expression, bmp4 (green) expression, and BMP signaling domain (red circles) in different animal models.(B and C) Schematic representation of NvDpp, NvBMP5-8, NvGDF5-like, NvChd, NvGrm, NvGbx, and Hox expression domains in planula viewed laterally and orally. Red lines, cutting planes; black double-headed arrows, directive axis; asterisks, blastopore.(D–K) The αpSMAD1/5 and αNvHoxE antibody staining in control and morphant early planulae, n > 50 for each sample; (D–I) lateral views; (J and K) oral views; asterisks, blastopore. (D) αpSMAD1/5-positive nuclei are located on NvHoxE-expressing side. αpSMAD1/5 and αNvHoxE stainings partially overlap. (E–K) αpSMAD1/5 and αNvHoxE in StdMO, ChdMO, GrmMO, GDF5lMO, BMP5-8MO, and DppMO embryos. Staining is absent in DppMO, BMP5-8MO, and ChdMO and suppressed (white arrow) in GDF5lMO (E–H); the domain showing strong staining (white double-headed arrows and white demarcating lines) is narrower in the StdMO than in the GrmMO (J and K).See also .
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