BMPs and Chordin regulate patterning of the directive axis in a sea anemone

Abstract

The TGF-␤ 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.axis formation ͉ BMP signaling ͉ Cnidaria ͉ evolution ͉ Nematostella

On growth and form: a Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes

“…These define a second axis, termed the directive axis, which is orthogonal to the primary oralaboral axis. Intriguingly, asymmetric BMP expression has been documented in Acropora and Nematostella in gastrulating embryos at one side of the blastopore, prefiguring the directive axis (Hayward et al, 2002;Finnerty et al, 2004;Saina et al, 2009). Surprisingly, however, a chordin homolog is expressed on the same side as BMPs in Nematostella Rentzsch et al, 2006), raising the question of whether this BMP-Chordin system acts in a fashion homologous to that in chordates or Drosophila in secondary body axis specification.…”

“…Wnt signaling inhibits Gsk3, thereby also stabilizing Smad1 and thus promoting BMP signaling (Fuentealba et al, 2007). Primary and secondary axis regulation is also linked in Nematostella, as the RNAi-mediated BMP depletion affects both the directive and the oral-aboral axis (Saina et al, 2009). Interestingly, the Wnt-BMP double gradient also seems to have been evolutionarily co-opted for organ formation, for example in DV and AP patterning in the Drosophila wing disc (Strigini and Cohen, 1999).…”

“…Surprisingly, however, a chordin homolog is expressed on the same side as BMPs in Nematostella Rentzsch et al, 2006), raising the question of whether this BMP-Chordin system acts in a fashion homologous to that in chordates or Drosophila in secondary body axis specification. Recent elegant antisense morpholino experiments by Technau and colleagues show that, as in Xenopus (De Robertis, 2009), BMP and Chordin interact in a double-negative feedback loop in Nematostella (Saina et al, 2009); despite being expressed on the same side as BMP, chordin could still generate a BMP signaling gradient. In Xenopus, it has been shown that Chordin has different diffusion rates to BMP, and that the ability of Chordin to bind and inhibit BMPs can be regulated by Crossveinless 2 and Tolloid proteases (De Robertis, 2009a;Umulis et al, 2009); both these features can generate graded BMP signaling.…”

Evolutionary crossroads in developmental biology: Cnidaria

“…After about a week, the planula (see Glossary, Box 1) settles and metamorphoses into a polyp, which reaches sexual maturity in 3-6 months (Fritzenwanker and Technau, 2002;Hand and Uhlinger, 1992). The ease of culturing and maintaining Nematostella in the laboratory (Fritzenwanker and Technau, 2002;Genikhovich and Technau, 2009) has greatly facilitated its use as a developmental system.…”

Position matters: Variability in the spatial pattern of BMP modulators generates functional diversity

“…BMP/Dpp Against the Source: Lessons From Planarians, Spiders, Crustaceans, and Beetles Recent analysis of BMPs and its modulators in planarians (Lophotrochozoan), echinoderms (basal deuterostome), spiders, crustaceans, and beetles (arthropods) have broadened our understanding of the role of this pathway during embryogenesis (Akiyama-Oda and Oda, 2006;Duboc et al, 2004;Fritsch et al, 2010;Gavino and Reddien, 2011;Lapraz et al, 2009;Molina et al, 2011;Nunes da Fonseca et al, 2010;Park et al, 2010;Reddien et al, 2007;Saina et al, 2009;van der Zee et al, 2006). In all these studies not only dpp expression was analyzed, but also the activity of Dpp signaling using antibodies against pMad was visualized.…”