The Wnt code: cnidarians signal the way

Abstract

Cnidarians are the simplest metazoans with a nervous system. They are well known for their regeneration capacity, which is based on the restoration of a signalling centre (organizer). Recent work has identified the canonical Wnt pathway in the freshwater polyp Hydra, where it acts in organizer formation and regeneration. Wnt signalling is also essential for cnidarian embryogenesis. In the sea anemone Nematostella vectensis 11 of the 12 known wnt gene subfamilies were identified. Different wnt genes exhibit serial and overlapping expression domains along the oral-aboral axis of the embryo (the 'wnt code'). This is reminiscent of the hox code (cluster) in bilaterian embryogenesis that is, however, absent in cnidarians. It is proposed that the common ancestor of cnidarians and bilaterians invented a set of wnt genes that patterned the ancient main body axis. Major antagonists of Wnt ligands (e.g. Dkk 1/2/4) that were previously known only from chordates, are also present in cnidarians and exhibit a similar conserved function. The unexpectedly high level of genetic complexity of wnt genes evolved in early multi-cellular animals about 650 Myr ago and suggests a radical expansion of the genetic repertoire, concurrent with the evolution of multi-cellularity and the diversification of eumetazoan body plans. Oncogene (2006Oncogene ( ) 25, 7450-7460. doi:10.1038 Keywords: Wnt signalling; regeneration; axis formation; Hydra; Nematostella; cnidaria Cnidarians are genetically complexThe Cnidaria is an ancient metazoan phylum of diploblastic animals including freshwater polyps and hydroids, sea anemones and corals, and jellyfish. All cnidarians share the same simple body plan that is reminiscent of an early bilaterian gastrula. However, they are lacking the mesoderm and possess only two germ layers, an outer ectoderm and inner endoderm that are separated by an acellular mesogloea. Cnidaria are a sister-group to the Bilateria (Figure 1), and the fossil record reveals that cnidarians are >500 Myr old (Chen et al., 2000(Chen et al., , 2002Conway Morris, 2000). They are of crucial importance for unravelling the origin and evolution of major signalling pathways in animal evolution.There are two major genetic model systems for cnidarians: the well-known freshwater polyp Hydra (Steele, 2006) and the starlet sea anemone Nematostella vectensis (Holland, 2004;Darling et al., 2005), which was introduced by the pioneering work of Cadet Hand (Hand and Uhlinger, 1992). Recent EST projects in these and some other cnidarian taxa have revealed an astonishing and unexpected genetic complexity of cnidarians. Analyses of ESTs from the anthozoans Acropora millepora and Nematostella vectensis have lead to the identification of 16 571 non-redundant ESTs and 12 547 predicted peptides across the two species (7484 from Nematostella and 5063 from Acropora (Miller et al., 2005;Technau et al., 2005). Both data sets are far from saturation and one can estimate that anthozoan genomes are likely to contain 25 000 genes, which is in the same range as vertebr...

-Catenin-Dependent Wnt Signaling in C. elegans: Teaching an Old Dog a New Trick

“…The C. elegans genome contains only five genes encoding Wnt ligands: lin-44, egl-20, mom-2, cwn-1, and cwn-2 (Shackleford et al 1993;Herman et al 1995;Rocheleau et al 1997;Thorpe et al 1997;Maloof et al 1999), a lower number than in other animals. It may have once been assumed this small number was due to some "lower" evolutionary status of nematodes, but genome sequencing of diverse animal species now suggests that the early metazoan common ancestor had a large complement of Wnt genes and that nematode lineages have lost many of these genes (Guder et al 2006;van Amerongen and Nusse 2009;Janssen et al 2010;Pang et al 2010). Surprisingly, only one of the C. elegans Wnts, MOM-2, appears to play a major role during embryogenesis: 70% of mom-2 zygotic mutant animals die during embryogenesis, whereas ,5% of lin-44; cwn-1; cwn-2 or lin-44; cwn-1; egl-20 mutants display embryonic lethality (Thorpe et al 1997;Gleason et al 2006).…”

“…This evolutionary conservation suggests that cellular signaling mechanisms functioning in response to Wnts were part of the "developmental toolkit" in place at least 500 million years ago in the common ancestor to modern metazoans (Guder et al 2006). Signaling regulated by Wnt ligand binding plays an important and often essential role in an astounding number of processes during invertebrate and vertebrate development, as well as functioning in the maintenance of adult stem cell populations in vertebrates and Drosophila (reviewed in Clevers 2006;Cadigan and Peifer 2009;MacDonald et al 2009).…”

Frizzled and LRP5/6 Receptors for Wnt/ -Catenin Signaling

“…As such, mutations in the Wnt pathway cause many diseases including cancer (Clevers 2006). All of the above "core" Wnt/b-catenin signaling components are present in vertebrates and the well-studied fruit fly Drosophila and are also encoded in sequenced genomes of radial symmetric Cnidarians Hydra magnipapillata and Nematostella vectensis (Guder et al 2006) and of the primitive metazoan sponge Amphimedon queenslandica …”

“…As such, mutations in the Wnt pathway cause many diseases including cancer (Clevers 2006). All of the above "core" Wnt/b-catenin signaling components are present in vertebrates and the well-studied fruit fly Drosophila and are also encoded in sequenced genomes of radial symmetric Cnidarians Hydra magnipapillata and Nematostella vectensis (Guder et al 2006) and of the primitive metazoan sponge Amphimedon queenslandica (Adamska et al 2010). Gene loss is prevalent in the genome of nematodes, such as the popular model organism Caenorhabditis elegans, which appears to lack an ortholog of LRP5/6 (Phillips and Kimble 2009).…”

Entre homéostasie et développement, quelles stratégies pour régénérer ?

“…En particulier dans les deux modèles, il est possible d'éteindre spécifiquement mais transitoirement l'expression de gènes grâce à l'ARN interférence, obtenue en nourrissant les animaux avec des bactéries qui produisent des ARNs double-brin (Newmark et al, 2003;Reddien et al, 2005;Chera et al, 2006;Buzgariu et al, 2008). Dans les deux systèmes, le séquençage de collections d'ADNc et de séquences génomiques a mis en évidence la grande conservation des cascades de signalisation au sein des eumétazoaires (Guder et al, 2006;Sanchez Alvarado & Tsonis, 2006;Chapman et al, 2010). Par ailleurs chez l'Hydre, des lignées transgéniques peuvent être produites, permettant ainsi de suivre le remodelage cellulaire induit par bissection (Wittlieb et al, 2006;Khalturin et al, 2007).…”