The expression of Delta ligands in the sponge Amphimedon queenslandica suggests an ancient role for Notch signaling in metazoan development
© Richards and Degnan; licensee BioMed Central Ltd. 2012
Received: 8 May 2012
Accepted: 27 June 2012
Published: 23 July 2012
Intercellular signaling via the Notch pathway regulates cell fate, patterning, differentiation and proliferation, and is essential for the proper development of bilaterians and cnidarians. To investigate the origins of the Notch pathway, we are studying its deployment in a representative of an early branching lineage, the poriferan Amphimedon queenslandica. The A. queenslandica genome encodes a single Notch receptor and five membrane-bound Delta ligands, as well as orthologs of many genes that enact and regulate canonical Notch signaling events in other animals.
In the present report we analyze the structure of the five A. queenslandica Deltas using bioinformatic methods, and characterize their developmental expression via whole mount in situ hybridization and histological staining.
Sequence analysis of the A. queenslandica Delta ligands highlights the conservation of their extracellular domains. This contrasts with the divergence of their intracellular regions, each of which is predicted to bear a unique repertoire of protein interaction motifs. In keeping with this diversity, these ligands are expressed differentially and dynamically throughout A. queenslandica embryogenesis, both in cell type specific patterns and broader regional domains. Notably, this expression coincides with the development of the photosensitive larval pigment ring, the non-ciliated cuboidal cells located at the anterior pole of the larva, and the intraepithelial flask cells and globular cells that are presumed to have sensory and/or secretory roles.
Based on the dynamic and complex patterns of expression of these Delta ligands and the Notch receptor, we propose that the Notch signaling pathway is involved in regulating the development of diverse cell types in A. queenslandica. From these observations we infer that Notch signaling is a conserved feature of metazoan development, ancestrally contributing to cell determination, patterning and differentiation processes.
Intercellular signaling pathways drive animal development by facilitating cellular communication and the coordination of morphogenetic processes. Of the major developmental signaling pathways, comparative studies have revealed that core components of the Wnt, Notch, transforming growth factor β (TGFβ) and receptor tyrosine kinase (RTK) pathways are encoded in the genomes of representative species from all major extant animal clades[1, 2]. Here, we focus on the evolution of one of these pathways, the Notch signaling pathway, which provides a mechanism for short-range, localized signaling between directly apposing cells (reviewed in[3–5]).
At the molecular level, a Notch signaling event is initiated by the binding of a Delta/Serrate type ligand to the Notch receptor. In response, the receptor undergoes a series of proteolytic cleavages that results in the production of a short intracellular signaling fragment, the Notch intracellular domain (NICD). The NICD then translocates to the nucleus of the receiving cell, where it binds to the CBF1/Suppressor of hairless/Lag1 (CSL) repressor complex and elicits a change in the transcriptional activity of the cell. Commonly, Notch signaling events act to regulate the responsiveness of individual cells, or cell populations, to the developmental instructions they encounter. In this capacity, Notch signaling has been shown to direct cell specification, differentiation and proliferation, delineate boundaries between developmental fields, and regulate cell migration and apoptotic events (reviewed in[3, 7]).
Broad-ranging examples of Notch pathway activity have been described in bilaterians, and recent studies in the Cnidaria have implicated Notch signaling in the differentiation of the interstitial cell lineage and boundary formation in the hydrozoan Hydra, and in nervous system development of the anthozoan Nematostella vectensis[8–11]. These reports of canonical Notch signaling in Cnidaria indicate that the eumetazoan ancestor also likely deployed the Notch pathway in a range of developmental processes.
Here, we analyze the sequence and developmental expression of Delta and Notch genes in the demosponge Amphimedon queenslandica and thereby contribute to the understanding of the role of this signaling pathway in earlier branching metazoan clades, that is, Porifera, Ctenophora and Trichoplax[12, 13]. Previously, we and others have reported that the genome of A. queenslandica encodes the molecular components of the canonical Notch pathway, including ligands, a receptor and CSL transcription factor, as well as many genes with a role in Notch activation, regulation and inhibition[14, 15]. We have also described the expression of the A. queenslandica Notch receptor and a single ligand, AmqDelta1, during the ontogeny of the globular cell lineage in late embryonic stages. In this report, we expand our analysis by documenting the expression of the Notch receptor and five Delta ligands across A. queenslandica embryogenesis. We describe the molecular structure of the five Delta genes in detail, and discuss the possible functional significance of their diversification. In addition, we present histological sections to describe A. queenslandica development in greater detail, and better contextualize the gene expression patterns. This study reveals a highly dynamic and complex pattern of Notch and Delta expression, consistent with Notch signaling playing a role in morphogenesis and cell fate determination in this demosponge.
Sequence analysis of A. queenslandica Deltas
The phylogenetic relationships between A. queenslandica Delta ligands and other metazoan Notch ligands have been analyzed elsewhere. Briefly, the A. queenslandica Deltas group with all other metazoan Deltas to the exclusion of all Jagged type ligands. AmqDelta1, 2, 4 and 5 form a monophyletic clade, whereas AmqDelta3 lies within a poorly resolved clade, which also includes sequences from Lottia Strongylocentrotus and Helobdella. As poor resolution of DSL phylogenies is common, it has been suggested that analysis of the number and spacing of the cysteine residues in the EGF repeat domains of the ligands can be informative about their relationships. In this way, EGF repeats are annotated 1 to 4 on the basis of their cysteine arrangements, and an ancestral EGF organization in Delta proteins has been proposed for the Bilateria (Figure1B). AmqDelta3 has an EGF repeat pattern most similar to that of bilaterians, suggesting that it has retained a more ancestral domain arrangement while the other ligands have diverged from this organization (Figure1B).
All ligands are predicted to possess a variety of functional linear motifs in their intracellular tails (ICT) (Figure1B). All contain multiple lysines in their ICTs, as well potential phosphorylation sites, although only AmqDeltas2 to 4 also have residues that could be sites for glycosaminoglycan attachments, and only AmqDeltas2 and 3 have sites that may be N-glycosylated. All ligands also contain PDZ domain binding sites, and all except AmqDelta1 have sites that may interact with the adaptor protein complex. Several ligands also possess WW domain binding motifs, and a number of Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domain binding sites are proposed in AmqDeltas1 to 4 and AmqDeltas2 to 5 respectively. Src Homology 3 (SH3) domain binding sites are predicted in AmqDeltas2 to 4 and a tumor necrosis factor receptor associated factor (TRAF) binding site is predicted in AmqDelta3 only. These data should be interpreted with the caveat that hits returned by ELM are not assigned significance and are only intended to act as a guide to sites of interest. Nonetheless, it appears that each of the five AmqDelta proteins possesses a unique repertoire of interaction sites in its intracellular domain.
Developmental expression of the A. queenslandica Notch receptor and ligands
Cytological context of A. queenslandica Notch/Delta expression
Prior to pigment spot formation, there is no distinctive cell population found specifically at the future position of the posterior ciliated cells (Figure8A). By spot stage, cells just anteriolateral to the pigment spot are distinguished from the surrounding epithelial cells due to their columnar morphology and alignment (Figure8A’), coincident with the spatial expression of AmqNotch and AmqDelta4 at this stage (Figures 5B and7B). In late ring embryos, these cells have further elongated internally, and are polarized; nuclei are basal, cilia are apical and the cells are in small clusters (Figure8A”). The expression of AmqNotch and AmqDelta4 is now also seen in a narrower domain that lies just below the surface of the embryo (Figures 5D,D’ and 7E’). The larval expression of AmqDelta4 remains in the region under the pigment ring, the presumptive location of the nuclei of the cells bearing the long posterior cilia (Figure5E).
At the anterior pole of the A. queenslandica larva is a cluster of cuboidal non-ciliated cells. At cloud stage, a distinct cell population is already visible in the vicinity of the anterior pole (Figure8B), at a time in which AmqDelta4 expression is noted in this region, while AmqDelta3 is located to the interior (Figures 4B and5A). By spot stage, a group of cells, morphologically similar to those seen in the area during the cloud stage, are condensing into a cluster at the anterior pole (Figure8B’), both AmqDelta1 and AmqDelta4 are expressed at this pole (Figures 2C,C” and 5B). In the ring stage embryo, the anterior pole is clearly distinguished from the surrounding ciliated epithelial cells (Figure8B”); AmqDelta1 is still expressed at the anterior pole (Figure2D).
The A. queenslandica embryo is initially organized into two layers during development from brown to spot stages; a third layer becomes evident in the transition from spot to larva. At the cloud/spot stage, the inner layer is comprised of large granular macromeres while the outer layer contains both micromeres and large globular macromeres (Figure8C). Most of the ligands are expressed in patterns that would suggest their localization to cells belonging to the large macromere population, predominantly in the outer layer, and around the boundary between the two layers (Figures 2A,B,3B,C,4B,C and5A,B). By the ring stage, the outer layer contains no macromeres, being comprised only of epithelial cells, interspersed with flask cells (Figure8C’). The inner layer consists of a mixture of large macromeres and various unidentified cell types (Figure8C’). At this point in development, all genes except AmqDelta5 are localized to the region in which the middle layer is forming (Figures 2D,3D,4D,5C and7E). In the larva, three cells layers are evident: an outer epithelial layer interspersed with globular cells and flask cells; a subepithelial layer, composed mostly of large macromeres running in a perpendicular orientation to the anterior-posterior axis; and an inner cell mass in which spicule-containing sclerocytes and amoeboid cell types are embedded in a dense collagenous matrix (Figure8C”). AmqDelta3 remains expressed in the larval subepithelial layer (Figure4F).
Uniquely, AmqDelta2 is strongly expressed directly under the forming pigment spot (Figure3B,C). A distinct cell population is not noted in this region, however in cloud (not shown) and spot stage embryos, the inner layer macromeres are more densely packed in this area (Figure8D).
The larval epithelial layer is composed of ciliated columnar cells interspersed with flask cells and globular cells. Flask cells appear amongst the anterior third of the epithelial layer in ring and late ring embryos (Figure8E), coincident with AmqDelta2 and 4 expression in isolated cells around the anterior periphery (Figures 3D and5D). In the larva, (Figure8E’), AmqDelta1 and 4 are expressed in patterns that suggest they are localized to the globular cells and flask cells respectively (Figures 2F and5E). The globular cells, expressing AmqDelta1, are found around the entire larva and appear to migrate to this position from the subepithelial layer during the ring stage, as previously described (Figure2E).
Here, we describe the structure and expression patterns of five Delta ligands and the Notch receptor throughout the embryonic development of the demosponge Amphimedon queenslandica, building upon our previous analysis of AmqNotch and AmqDelta1 in the ontogeny of one larval cell type, the globular cell. The more detailed and comprehensive characterization of Notch and Delta expression in this current study reveals a likely contribution of the Notch signaling pathway to the orchestration of a number of aspects of A. queenslandica development.
Ligand function and evolution
It is probable that there was a single Delta-type ligand in the metazoan last common ancestor (LCA), with the Jagged/Serrate-type ligands being added to the pathway in the stem lineage of the Cnidaria + Bilateria. The independent diversification of Deltas in A. queenslandica and in other metazoan lineages (for example, Lottia gigantea, seven ligands; Caenorhabditis elegans, ten ligands) reflects a general theme in the evolvability of signaling pathway ligands. The deeper relationships of Notch ligands generally are not well resolved, or do not reflect accepted animal phylogenies[15, 18, 21]. Due to their more recent shared ancestry, it is not unexpected that bilaterian ligands share features to the exclusion of the AmqDeltas. As well as the number and location of the EGF and DOS domains (Figures 1B, Additional file2), essential binding sites identified in bilaterian DSL domains are not conserved in the A. queenslandica ligands.
When considering the functional significance of A. queenslandica possessing five Delta ligands, and the possible interactions of these Deltas with the single Notch receptor, it is worth noting that Notch ligands are known to partake in diverse interactions outside of the canonical signaling context. For example, homotypic ligand-ligand interactions can play a role in cell adhesiveness, and ligands may be cleaved and released to act as soluble agonists or antagonists of signaling. Further, the Notch pathway can be negatively regulated via cis inhibition, in which ligands sequester receptor molecules intracellularly, or via the binding of dominant-negative forms of ligands that lack intracellular regions. Although this latter effect was reported using engineered versions of truncated ligands, it is noteworthy that AmqDelta1 similarly has a highly reduced intracellular domain (Figure1B).
The role of multiple ligands may also be to facilitate the activation of reciprocal events in the signaling cell as a result of receptor/ligand binding. Such an effect could be exerted by the binding capacities of the ligand intracellular tails[28, 29]. In bilaterians, the intracellular regions of DSL ligands are divergent and do not contain any globular domains, however they commonly possess lysine residues and a C-terminal PDZ domain binding motif. These features enable interactions with PDZ-containing scaffold/adaptor proteins[30, 31], as well as providing sites for ubiquitination and thus endocytotic regulation of ligands[32, 33]. The intracellular tails of the A. queenslandica Deltas are similarly highly divergent, and are also predicted to contain multiple sites for ubiquitination as well as a variety of short linear motifs capable of binding to PDZ, PTB, SH2 and SH3 domains, amongst others (Figure1B). This diversity may thus provide a variable interface for interactions between each ligand and the protein populations of signaling cells.
Notch pathway expression in A. queenslandica development
Three modes of activity are classically described for the Notch signaling pathway: lateral inhibition, boundary formation and asymmetric lineage decisions. We find that the developmental expression patterns of Notch and its ligands in A. queenslandica are reminiscent of some of these classical Notch processes. In lateral inhibition, Notch signaling within equivalence groups singles out cells that will then follow a different developmental trajectory to the original population. Accordingly, we propose that the cell-type-restricted expression domains of the A. queenslandica Deltas may reflect Notch activity in shaping the development of these particular cell lineages to the exclusion of their neighboring cells (for example, AmqDelta1, anterior pole cells Figure 2D; AmqDelta4, flask cells Figure 5D). Regarding boundary formation, we propose that Notch signaling plays a role in determining the identity of the posterior ciliated cells that arise in a precise ring surrounding the pigment spot in A. queenslandica. In this region, the expression of AmqNotch and AmqDelta4 are coincident with the morphological differentiation of the ciliated cells, which differentially express the cryptochrome-encoding gene Aq-Cry2 (Figures 5B7C and8A). For the third mode of Notch activity, asymmetric lineage decisions, we are unable to determine whether there is asymmetric segregation of these molecules based on the expression of the ligands and receptor alone. The early divisions of blastomeres in A. queenslandica are certainly highly asymmetric, however we found no significant expression of Notch components during these stages.
Homology of metazoan cell types based on Notch/Delta expression
Given the highly pleiotropic and context-dependent nature of Notch signaling, and the widespread co-option of signaling pathways into the generation of lineage-specific characters (see for example), caution is required when proposing cell homologies between sponges and eumetazoans based solely on the localized enrichment of Delta and Notch transcripts. However, it is intriguing that many of the cells expressing Deltas in A. queenslandica may perform sensory functions in the larva, as a key role of Notch signaling in Eumetazoa is consistently in the specification, determination and differentiation of neural cell types[8, 11, 18, 27, 38–40]. A. queenslandica larval flask cells, which express AmqDelta3 and 4, are morphologically most akin to eumetazoan sensory cells, possessing a cilium that arises from a deep invagination in the cell and a basal nucleus that is surrounded by electron-lucent vesicles[20, 41]. In contrast the globular cells, which express AmqDelta1, do not display conventional sensory morphology yet have previously been shown to express an ortholog of atonal, a basic helix-loop-helix (bHLH) neurogenic transcription factor, and components of the post-synaptic density. The anterior pole cells (AmqDelta1 and 4), also express a number of bHLH orthologs involved in neural development including atonal and acheate-scute (GSR and BMD, unpublished results) and due to their position, are likely to be involved in the settlement response of the larva. The posterior ciliated cells (AmqDelta4), the only cells for which a sensory function has been explicitly confirmed[20, 35, 44], also express acheate-scute (Richards and Degnan unpublished), a homeobox gene with neural functionality (LIM), and components of the WNT, TGFβ and Hedgehog signaling pathways[34, 36, 46]. That this suite of sponge larval cells expresses Delta ligands and other genes related to the development of neural cell types suggests a shared ancestry between non-neural sensory cells of poriferans and the neurons of the Eumetazoa.
The embryonic expression domains of several A. queenslandica Notch ligands persist into the larval period: for example, AmqDelta1, globular cells; AmqDelta4, posterior ciliated cells. This is in contrast to the transient ligand activity commonly reported in bilaterians, in which Delta expression occurs during the specification and/or differentiation of cell types, but then ceases once morphogenesis is complete[18, 27, 38, 39, 47]. In sponges, cellular plasticity, rather than ‘point-of-no-return differentiation’, is a widespread feature, for example, larval epithelial cells dedifferentiate at metamorphosis and then redifferentiate into choanocytes in A. queenslandica. The persistence of Delta signaling in some of the larval sponge cells may therefore be required to maintain cellular identity in lieu of these cells achieving a terminally differentiated state.
Based on our own and other studies of the Notch pathway in A. queenslandica, we propose that the origin of this signaling mechanism can be minimally dated to the last common ancestor of the Demospongiae + Eumetazoa (this study,[1, 14, 15]). Whether this ancestor was also the metazoan LCA awaits resolution of branching orders at the base of the animal kingdom. Although we do not have functional confirmation of this hypothesis, the diverse structures of the AmqDelta ligands, and their coincident expression in the development of multiple cell types and regions in the larva, strongly suggests that Notch signaling plays an active role in A. queenslandica development.
The expression of Delta ligands in many A. queenslandica cell types before they have achieved their final morphologies and/or locations, leads us to propose that a conserved facet of Notch signaling in A. queenslandica is to mediate the choices made by non-terminally differentiated cells. As such, Notch may be playing a developmental role by regulating the deployment of various cell differentiation gene batteries within the developing sponge embryo.
AmqNotch and AmqDelta1 have been previously reported. AmqDelta2 to 5 were identified in the A. queenslandica trace archives (http://blast.ncbi.nlm.nih.gov/Blast.cgi [Reniera_sp__jgi-2005_WGS]) by conducting tBLASTn searches using the conserved DSL domain of bilaterian Notch ligands. Traces recovered from these searches were assembled using an in-house assembly tool. Primers were designed to each identified DSL domain and used in RACE reactions to obtain full-length coding sequences (BD Smart Kit, Clontech Laboratories, Mountain View, CA, U.S.A). cDNA templates for RACE were synthesized from RNA isolated from A. queenslandica developmental stages. (Genbank accession numbers: AmqNotch, EU273942; AmqDelta1, EU273941; AmqDelta2, GU385841; AmqDelta3, GU385842; AmqDelta4, GU385843; AmqDelta5, GU385844.)
Delta proteins from representative metazoan species were aligned to the conceptually translated A. queenslandica sequences using MUSCLE, and manually edited in SEAVIEW. Conserved domain predictions were made using InterProScan (EBI); Delta EGF repeats and Delta/OSM-11 (DOS) motifs were manually annotated following the standards of Rasmussen et al. and Komatsu respectively.
For analysis of functional sites in the intracellular tails of AmqDelta protein sequences the ELM (Eukaryotic Linear Motif) server was used. ELM results are filtered by species, but as sponges are not represented in the ELM organism menu, analyses were conducted using the Homo sapiens filter and then the Drosophila melanogaster filter and only sites retrieved by both analyses were retained.
Whole mount in situ hybridization
Adult sponges were collected from Heron Island Reef (latitude: 23° 26′ 60 S, longitude: 151° 55′ 0 E, Great Barrier Reef, Australia) and developmental material was procured following. Whole mount in situ hybridizations were carried out as described in using digoxigenin-labeled RNA probes transcribed from PCR fragments that had been cloned into the pGemT vector (Promega, Madison, WI, U.S.A). Probe length and domain coverage: AmqDelta1, 900 bp, DSL + EGF; AmqDelta2, 760 bp, 5′ untranslated region (UTR) + DSL + EGF; AmqDelta3, 1.9 kb, DSL + EGF + TM; AmqDelta4, 960 bp, 5′UTR + DSL; AmqDelta5, 875 bp, DSL + EGF; AmqNotch, 3 kb, Notch/Lin repeats (NLR) + Ankyrin domains (ANK).
Developmental stages were fixed and sectioned as described in. Hemotoxylin and eosin staining of sectioned material was carried out as described in with minor modifications. Images were captured using a Nikon Digital Sight DS-U1 camera (Nikon Australia Pty. Ltd. Lidcombe, Australia) mounted on an Olympus BX60F-3 compound microscope (Olympus Australia Pty. Ltd., Mt Waverly, Australia) with Nomarski optics. Adobe Photoshop CS2 (version 9.0.2) (Adobe Systems Inc., San Jose, CA, U.S.A.) was used to edit images for publication.
GSR: present address: Sars International Centre for Marine Molecular Biology, Bergen 5008, Norway.
We thank Erica Lovas for cutting the A. queenslandica sections. This research was supported by grants to BMD from the Australian Research Council.
- Richards GS, Degnan BM: The dawn of developmental signaling in the Metazoa. Cold Spring Harb Symp Quant Biol. 2009, 74: 81-90. 10.1101/sqb.2009.74.028.View ArticlePubMedGoogle Scholar
- Srivastava M, Simakov O, Chapman J, Fahey B, Gauthier MEA, Mitros T, Richards GS, Conaco C, Dacre M, Hellsten U, Larroux C, Putnam NH, Stanke M, Adamska M, Darling A, Degnan SM, Oakley TH, Plachetzki D, Zhai Y, Adamski M, Calcino A, Cummins SF, Goodstein DM, Harris C, Jackson D, Leys SP, Shu S, Woodcroft BJ, Vervoort M, Kosik KS, Manning G, Degnan BM, Rokhsar DS: The Amphimedon queenslandica genome and the evolution of animal complexity. Nature. 2010, 466: 720-726. 10.1038/nature09201.PubMed CentralView ArticlePubMedGoogle Scholar
- Bray SJ: Notch signaling: a simple pathway becomes complex. Nat Rev Mol Cell Biol. 2006, 7: 678-689. 10.1038/nrm2009.View ArticlePubMedGoogle Scholar
- Kopan R, Ilagan MXG: The canonical Notch signaling pathway: unfolding the activation mechanism. Cell. 2009, 137: 216-233. 10.1016/j.cell.2009.03.045.PubMed CentralView ArticlePubMedGoogle Scholar
- Andersson ER, Sandberg R, Lendahl U: Notch signaling: simplicity in design, versatility in function. Development. 2011, 138: 3593-3612. 10.1242/dev.063610.View ArticlePubMedGoogle Scholar
- Artavanis-Tsakonas S, Matsuno K, Fortini ME: Notch signaling. Science. 1995, 14: 225-232.View ArticleGoogle Scholar
- Lai EC: Notch signaling: control of cell communication and cell fate. Development. 2004, 131: 965-973. 10.1242/dev.01074.View ArticlePubMedGoogle Scholar
- Kasbauer T, Towb P, Alexandrova O, David CN, Dall’Armi E, Staudigl A, Stiening B, Bottger A: The Notch signaling pathway in the cnidarian Hydra. Dev Biol. 2007, 303: 376-390. 10.1016/j.ydbio.2006.11.022.View ArticlePubMedGoogle Scholar
- Khalturin K, Anton-Erxleben F, Milde S, Plotz C, Wittlieb J, Hemmrich G, Bosch TC: Transgenic stem cells in Hydra reveal an early evolutionary origin for key elements controlling self renewal and differentiation. Dev Biol. 2007, 309: 32-44. 10.1016/j.ydbio.2007.06.013.View ArticlePubMedGoogle Scholar
- Münder S, Käsbauer T, Prexl A, Aufschnaiter R, Zhang X, Towb P, Böttger A: Notch signalling defines critical boundary during budding in Hydra. Dev Biol. 2010, 344: 331-345. 10.1016/j.ydbio.2010.05.517.View ArticlePubMedGoogle Scholar
- Marlow H, Roettinger E, Boekhout M, Martindale MQ: Functional roles of Notch signaling in the cnidarian Nematostella vectensis. Dev Biol. 2012, 362: 295-308. 10.1016/j.ydbio.2011.11.012.PubMed CentralView ArticlePubMedGoogle Scholar
- Dunn CW, Hejnol A, Matus DQ, Pang K, Browne WE, Smith SA, Seaver E, Rouse GW, Obst M, Edgecombe GD, Sørensen MV, Haddock SH, Schmidt-Rhaesa A, Okusu A, Kristensen RM, Wheeler WC, Martindale MQ, Giribet G: Broad phylogenomic sampling improves resolution of the animal tree of life. Nature. 2008, 452: 745-749. 10.1038/nature06614.View ArticlePubMedGoogle Scholar
- Philippe H, Derelle R, Lopez P, Pick K, Borchiellini C, Boury-Esnault N, Vacelet J, Renard E, Houliston E, Queinnec E, Da Silva C, Wincker P, Le Guyader H, Leys S, Jackson DJ, Schreiber F, Erpenbeck D, Morgenstern B, Woerheide G, Manuel M: Phylogenomics revives traditional views on deep animal relationships. Curr Biol. 2009, 19: 706-712. 10.1016/j.cub.2009.02.052.View ArticlePubMedGoogle Scholar
- Richards GS, Simionato E, Perron M, Adamska M, Vervoort M, Degnan BM: Sponge genes provide new insight into the evolutionary origin of the neurogenic circuit. Curr Biol. 2008, 18: 1156-1161. 10.1016/j.cub.2008.06.074.View ArticlePubMedGoogle Scholar
- Gazave E, Lapebie P, Richards GS, Brunet F, Ereskovsky AV, Degnan BM, Borchiellini C, Vervoort M, Renard E: Origin and evolution of the Notch signaling pathway: an overview from eukaryotic genomes. BMC Evol Biol. 2009, 9: 249-10.1186/1471-2148-9-249.PubMed CentralView ArticlePubMedGoogle Scholar
- Six E, Ndiaye D, Laabi Y, Brou C, Gupta-Rossi N, Israel A, Logeat F: The Notch ligand Delta1 is sequentially cleaved by an ADAM protease and γ-secretase. Proc Natl Acad Sci USA. 2003, 100: 7638-7643. 10.1073/pnas.1230693100.PubMed CentralView ArticlePubMedGoogle Scholar
- Panin VM, Shao L, Lei L, Moloney DJ, Irvine KD, Haltiwanger RS: Notch ligands are substrates for protein O-fucosyltransferase-1 and Fringe. J Biol Chem. 2002, 277: 29945-29952. 10.1074/jbc.M204445200.View ArticlePubMedGoogle Scholar
- Rasmussen SLK, Holland LZ, Schubert M, Beaster-Jones L, Holland ND: Amphioxus AmphiDelta: evolution of Delta protein structure segmentation and neurogenesis. Genesis. 2007, 45: 113-122. 10.1002/dvg.20278.View ArticlePubMedGoogle Scholar
- Puntervoll P, Linding R, Gemund C, Chabanis-Davidson S, Mattingsda M, Cameron S, Martin DMA, Ausiello G, Brannetti B, Costantini A, Ferre F, Maselli V, Via A, Cesareni G, Diella F, Superti-Furga G, Wyrwicz L, Ramu C, McGuigan C, Gudavalli R, Letunic I, Bork P, Rychlewski L, Kuster B, Helmer-Citterich M, Hunter WN, Aasland R, Gibson TJ: ELM server: a new resource for investigating short functional sites in modular eukaryotic proteins. Nucleic Acids Res. 2003, 31: 3625-3630. 10.1093/nar/gkg545.PubMed CentralView ArticlePubMedGoogle Scholar
- Leys SP, Degnan BM: Cytological basis of photoresponsive behaviour in a sponge larva. Biol Bull. 2001, 201: 323-338. 10.2307/1543611.View ArticlePubMedGoogle Scholar
- Lissemore JL, Starmer WT: Phylogenetic analysis of vertebrate and invertebrate Delta/Serrate/Lag-2 (DSL) proteins. Mol Phylo Evol. 1999, 11: 308-319. 10.1006/mpev.1998.0588.View ArticleGoogle Scholar
- Cordle J, Johnson S, Zi J, Tay Y, Roversi P, Wilkin MB, Hernández de Madrid B, Shimizu H, Jensen S, Whiteman P, Jin B, Redfield C, Baron M, Lea SM, Handford PA: A conserved face of the Jagged/Serrate DSL domain is involved in Notch trans-activation and cis-inhibition. Nat Struct Mol Biol. 2008, 15: 849-857. 10.1038/nsmb.1457.PubMed CentralView ArticlePubMedGoogle Scholar
- Fehon RG, Kooh PJ, Rebay I, Regan CL, Xu T, Muskavitch MA, Artavanis-Tsakonas S: Molecular interactions between the protein products of the neurogenic loci Notch and Delta two EGF-homologous genes in Drosophila. Cell. 1990, 61: 523-534. 10.1016/0092-8674(90)90534-L.View ArticlePubMedGoogle Scholar
- Qi H, Rand MD, Wu X, Sestan N, Wang W, Rakic P, Xu T, Artavanis-Tsakonas S: Processing of the notch ligand delta by the metalloprotease Kuzbanian. Science. 1999, 283: 91-94. 10.1126/science.283.5398.91.View ArticlePubMedGoogle Scholar
- Sun X, Artavanis-Tsakonas S: Secreted forms of DELTA and SERRATE define antagonists of Notch signaling in Drosophila. Development. 1997, 124: 3439-3448.PubMedGoogle Scholar
- Sakamoto K, Oharab O, Takagia M, Takedac S, Katsubea K: Intracellular cell-autonomous association of Notch and its ligands: a novel mechanism of notch signal modification. Dev Biol. 2002, 241: 313-326. 10.1006/dbio.2001.0517.View ArticlePubMedGoogle Scholar
- Chitnis A, Henrique D, Lewis J, Ish-Horowicz D, Kintner C: Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta. Nature. 1995, 375: 761-766. 10.1038/375761a0.View ArticlePubMedGoogle Scholar
- Pintar A, De Biasio A, Popovic M, Ivanova N, Pongor S: The intracellular region of Notch ligands: does the tail make the difference?. Biol Direct. 2007, 2: 19-10.1186/1745-6150-2-19.PubMed CentralView ArticlePubMedGoogle Scholar
- D’Souza B, Miyamoto A, Weinmaster G: The many facets of Notch ligands. Oncogene. 2008, 27: 5148-5167. 10.1038/onc.2008.229.PubMed CentralView ArticlePubMedGoogle Scholar
- Six EM, Ndiaye D, Sauer G, Laabi Y, Athman R, Cumano A, Brou C, Israel A, Logeat F: The notch ligand Delta1 recruits Dlg1 at cell–cell contacts and regulates cell migration. J Biol Chem. 2004, 279: 55818-55826. 10.1074/jbc.M408022200.View ArticlePubMedGoogle Scholar
- Wright GJ, Leslie JD, Ariza-McNaughton L, Lewis J: Delta proteins and MAGI proteins: an interaction of Notch ligands with intracellular scaffolding molecules and its significance for zebrafish development. Development. 2004, 131: 5659-5669. 10.1242/dev.01417.View ArticlePubMedGoogle Scholar
- Schweisguth F: Regulation of Notch signaling activity. Curr Biol. 2004, 14: R129-R138.View ArticlePubMedGoogle Scholar
- Nichols JT, Miyamoto A, Weinmaster G: Notch signaling-constantly on the move. Traffic. 2007, 8: 959-969. 10.1111/j.1600-0854.2007.00592.x.View ArticlePubMedGoogle Scholar
- Adamska M, Larroux C, Degnan SM, Green KM, Adamski M, Craigie A, Degnan BM: Wnt and TGF-β expression in the sponge Amphimedon queenslandica and the origin of metazoan embryonic patterning. PLoS One. 2007, 2: e1031-10.1371/journal.pone.0001031.PubMed CentralView ArticlePubMedGoogle Scholar
- Rivera AS, Ozturk N, Fahey B, Plachetzki DC, Degnan BM, Sancar A, Oakley TH: Blue light-receptive cryptochrome is expressed in a sponge eye lacking neurons and opsins. J Exp Biol. 2012, 215: 1278-1286. 10.1242/jeb.067140.PubMed CentralView ArticlePubMedGoogle Scholar
- Adamska M, Larroux C, Adamski M, Green K, Lovas E, Koop D, Richards GS, Zwafink C, Degnan BM: Conservation of Wnt pathway in the earliest branching multicellular animals sponges. Evol Dev. 2010, 12: 494-518. 10.1111/j.1525-142X.2010.00435.x.View ArticlePubMedGoogle Scholar
- Pires-daSilva A, Sommer RJ: The evolution of signaling pathways in animal development. Nat Rev Genet. 2003, 4: 39-49. 10.1038/nrg977.View ArticlePubMedGoogle Scholar
- Henrique D, Adam J, Myat A, Chitnis A, Lewis J, Ish-Horowicz D: Expression of a Delta homologue in prospective neurons in the chick. Nature. 1995, 375: 787-790. 10.1038/375787a0.View ArticlePubMedGoogle Scholar
- Stollewerk A: 2002 Recruitment of cell groups through Delta/Notch signaling during spider neurogenesis. Development. 2002, 129: 5339-5348. 10.1242/dev.00109.View ArticlePubMedGoogle Scholar
- Lu T, Luo Y, Yu J: BMP and Delta/Notch signaling control the development of amphioxus epidermal sensory neurons: insights into the evolution of the peripheral sensory system. Development. 2012, 139: 2020-2030. 10.1242/dev.073833.View ArticlePubMedGoogle Scholar
- Renard E, Vacelet J, Gazave E, Lapebie P, Borchiellini C, Ereskovsky AV: Origin of the neuro-sensory system: new and expected insights from sponges. Integ Zool. 2009, 4: 294-308. 10.1111/j.1749-4877.2009.00167.x.View ArticleGoogle Scholar
- Sakarya O, Armstrong KA, Adamska M, Adamski M, Wang I, Tidor B, Degnan BM, Oakley TH, Kosik KS: A post-synaptic scaffold at the origin of the animal kingdom. PLoS One. 2007, 2: e506-10.1371/journal.pone.0000506.PubMed CentralView ArticlePubMedGoogle Scholar
- Degnan SM, Degnan BM: The initiation of metamorphosis as an ancient polyphenic trait and its role in metazoan life-cycle evolution. Phil Trans R Soc B. 2010, 365: 653-669. 10.1098/rstb.2009.0253.View ArticleGoogle Scholar
- Leys SP, Degnan BM: Embryogenesis and metamorphosis in a haplosclerid demosponge: gastrulation and transdifferentiation of larval ciliated cells to choanocytes. Invert Biol. 2002, 121: 171-189.View ArticleGoogle Scholar
- Srivastava M, Larroux C, Lu DR, Mohanty K, Chapman J, Degnan BM, Rokhsar DS: Early evolution of the LIM homeobox gene family. BMC Biol. 2010, 8: 4-10.1186/1741-7007-8-4.PubMed CentralView ArticlePubMedGoogle Scholar
- Adamska M, Matus DQ, Adamski M, Green K, Rokhsar DS, Martindale MQ, Degnan BM: The evolutionary origin of hedgehog proteins. Curr Biol. 2007, 17: R836-R837. 10.1016/j.cub.2007.08.010.View ArticlePubMedGoogle Scholar
- Haenlin H, Kramatschek B, Campos-Ortega JA: The pattern of transcription of the neurogenic gene Delta of Drosophila melanogaster. Development. 1990, 110: 905-914.PubMedGoogle Scholar
- Müller WEG: The stem cell concept in sponges (Porifera): Metazoan traits. Sem Cell Dev Biol. 2007, 17: 481-491.View ArticleGoogle Scholar
- Edgar RC: MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinforma. 2004, 5: 113-10.1186/1471-2105-5-113.View ArticleGoogle Scholar
- Galtier N, Gouy M, Gautier C: SEAVIEW and PHYLO_WIN: two graphic tools for sequence alignment and molecular phylogeny. Comput Appl Biosci. 1996, 12: 543-548.PubMedGoogle Scholar
- Komatsu H: OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development. PLoS Biol. 2008, 6: e196-10.1371/journal.pbio.0060196.PubMed CentralView ArticlePubMedGoogle Scholar
- Leys SP, Larroux C, Gauthier M, Adamska M, Fahey B, Richards GS, Degnan SM, Degnan BM: Isolation of Amphimedon developmental material. CSH Protocols. 2008, 101101/pdbprot50.Google Scholar
- Larroux C, Fahey B, Adamska M, Richards GS, Gautheir M, Green K, Lovas E, Degnan BM: Whole-mount in situ hybridization in Amphimedon. CSH Protocols. 2008, 101101/pdbprot5096.Google Scholar
- Pasyk KA, Hassett CA: Modified hematoxylin and eosin staining method for epoxy-embedded tissue sections. Path Res Pract. 1989, 184: 635-638. 10.1016/S0344-0338(89)80170-0.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.