The evolutionary origin of hedgehog proteins (original) (raw)
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Developmental Biology, 2008
Hedgehog signaling is an important component of cell-cell communication during bilaterian development, and abnormal Hedgehog signaling contributes to disease and birth defects. Hedgehog genes are composed of a ligand ("hedge") domain and an autocatalytic intein ("hog") domain. Hedgehog (hh) ligands bind to a conserved set of receptors and activate downstream signal transduction pathways terminating with Gli/Ci transcription factors. We have identified five intein-containing genes in the anthozoan cnidarian Nematostella vectensis, two of which (NvHh1 and NvHh2) contain definitive hedgehog ligand domains, suggesting that to date, cnidarians are the earliest branching metazoan phylum to possess definitive Hh orthologs. Expression analysis of NvHh1 and NvHh2, the receptor NvPatched, and a downstream transcription factor NvGli (a Gli3/ Ci ortholog) indicate that these genes may have conserved roles in planar and trans-epithelial signaling during gut and germline development, while the three remaining intein-containing genes (NvHint1,2,3) are expressed in a cell-type-specific manner in putative neural precursors. Metazoan intein-containing genes that lack a hh ligand domain have previously only been identified within nematodes. However, we have identified intein-containing genes from both Nematostella and in two newly annotated lophotrochozoan genomes. Phylogenetic analyses suggest that while nematode inteins may be derived from an ancestral true hedgehog gene, the newly identified cnidarian and lophotrochozoan inteins may be orthologous, suggesting that both true hedgehog and hint genes may have been present in the cnidarian-bilaterian ancestor. Genomic surveys of N. vectensis suggest that most of the components of both protostome and deuterostome Hh signaling pathways are present in anthozoans and that some appear to have been lost in ecdysozoan lineages. Cnidarians possess many bilaterian cell-cell signaling pathways (Wnt, TGFβ, FGF, and Hh) that appear to act in concert to pattern tissues along the oral-aboral axis of the polyp. Cnidarians represent a diverse group of animals with a predominantly epithelial body plan, and perhaps selective pressures to pattern epithelia resulted in the ontogeny of the hedgehog pathway in the common ancestor of the Cnidaria and Bilateria.
The compact genome of the sponge Oopsacas minuta (Hexactinellida) is lacking key metazoan core genes
bioRxiv (Cold Spring Harbor Laboratory), 2022
Background: Bilaterian animals today represent 99% of animal biodiversity. Elucidating how bilaterian hallmarks emerged is a central question of animal evo-devo and evolutionary genomics. Studies of non-bilaterian genomes have suggested that the ancestral animal already possessed a diversified developmental toolkit, including some pathways required for bilaterian body plans. Comparing genomes within the early branching metazoan Porifera phylum is key to identify which changes and innovations contributed to the successful transition towards bilaterians. Results: Here, we report the first whole genome comprehensive analysis of a glass sponge, Oopsacas minuta, a member of the Hexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three other Porifera classes in terms of development, tissue organization, ecology and physiology. Although O. minuta does not exhibit drastic body simplifications, its genome is among the smallest animal genomes sequenced so far, surprisingly lacking several metazoan core genes (including Wnt and several key transcription factors). Our study also provided the complete genome of the symbiotic organism dominating the associated microbial community: a new Thaumarchaeota species. Conclusions: The genome of the glass sponge O. minuta differs from all other available sponge genomes by its compactness and smaller number of predicted proteins. The unexpected losses of numerous genes considered as ancestral and pivotal for metazoan morphogenetic processes most likely reflect the peculiar syncytial organization in this group. Our work further documents the importance of convergence during animal evolution, with multiple emergences of sponge skeleton, electrical signaling and multiciliated cells.
Gene, 2001
Recently the term Urmetazoa, as the hypothetical metazoan ancestor, was introduced to highlight the finding that all metazoan phyla including the Porifera (sponges) are derived from one common ancestor. Sponges as the evolutionarily oldest, still extant phylum, are provided with a complex network of structural and functional molecules. Analyses of sponge genomes from Demospongiae (Suberites domuncula and Geodia cydonium), Calcarea (Sycon raphanus) and Hexactinellida (Aphrocallistes vastus) have contributed also to the reconstruction of the evolutionary position of Metazoa with respect to Fungi. Furthermore, these analyses have provided evidence that the characteristic evolutionary novelties of Metazoa, such as the extracellular matrix molecules, the cell surface receptors, the nervous signal transduction molecules as well as the immune molecule existing in Porifera, share high sequence and in some aspects also functional similarities to related polypeptides found in other metazoan phyla. During the transition to Metazoa new domains occurred; as one example, the formation of the death domain from the ankyrin is outlined. In parallel, domanial proteins have been formed, such as the receptor tyrosine kinases. The metazoan essentials have been defined by analyzing and comparing the sponge sequences with the related sequences from the metazoans Homo sapiens, Caenorhabditis elegans and Drosophila melanogaster, the fungus Saccharomyces cerevisiae and the plant Arabidopsis thaliana. The data revealed that those sponge molecules grouped to cell adhesion cell recognition proteins are predominantly found in Protostomia and Deuterostomia while they are missing in Fungi and Viridiplantae. Moreover, evidence is presented allowing the conclusion that the sponge molecules are more closely related to the corresponding molecules from H. sapiens than to those of C. elegans or D. melanogaster. Especially surprising was the finding that the Demospongiae are provided with elements of adaptive immunity.
International Journal of Molecular Sciences
Hedgehog signaling is one of the key regulators of morphogenesis, cell differentiation, and regeneration. While the Hh pathway is present in all bilaterians, it has mainly been studied in model animals such as Drosophila and vertebrates. Despite the conservatism of its core components, mechanisms of signal transduction and additional components vary in Ecdysozoa and Deuterostomia. Vertebrates have multiple copies of the pathway members, which complicates signaling implementation, whereas model ecdysozoans appear to have lost some components due to fast evolution rates. To shed light on the ancestral state of Hh signaling, models from the third clade, Spiralia, are needed. In our research, we analyzed the transcriptomes of two spiralian animals, errantial annelid Platynereis dumerilii (Nereididae) and sedentarian annelid Pygospio elegans (Spionidae). We found that both annelids express almost all Hh pathway components present in Drosophila and mouse. We performed a phylogenetic analy...
PLoS ONE, 2007
Background. The origin of metazoan development and differentiation was contingent upon the evolution of cell adhesion, communication and cooperation mechanisms. While components of many of the major cell signalling pathways have been identified in a range of sponges (phylum Porifera), their roles in development have not been investigated and remain largely unknown. Here, we take the first steps toward reconstructing the developmental signalling systems used in the last common ancestor to living sponges and eumetazoans by studying the expression of genes encoding Wnt and TGF-b signalling ligands during the embryonic development of a sponge. Methodology/Principal Findings. Using resources generated in the recent sponge Amphimedon queenslandica (Demospongiae) genome project, we have recovered genes encoding Wnt and TGFb signalling ligands that are critical in patterning metazoan embryos. Both genes are expressed from the earliest stages of Amphimedon embryonic development in highly dynamic patterns. At the time when the Amphimedon embryos begin to display anterior-posterior polarity, Wnt expression becomes localised to the posterior pole and this expression continues until the swimming larva stage. In contrast, TGF-b expression is highest at the anterior pole. As in complex animals, sponge Wnt and TGF-b expression patterns intersect later in development during the patterning of a sub-community of cells that form a simple tissue-like structure, the pigment ring. Throughout development, Wnt and TGF-b are expressed radially along the anteriorposterior axis. Conclusions/Significance. We infer from the expression of Wnt and TGF-b in Amphimedon that the ancestor that gave rise to sponges, cnidarians and bilaterians had already evolved the capacity to direct the formation of relatively sophisticated body plans, with axes and tissues. The radially symmetrical expression patterns of Wnt and TGF-b along the anterior-posterior axis of sponge embryos and larvae suggest that these signalling pathways contributed to establishing axial polarity in the very first metazoans. Citation: Adamska M, Degnan SM, Green KM, Adamski M, Craigie A, et al (2007) Wnt and TGF-b Expression in the Sponge Amphimedon queenslandica and the Origin of Metazoan Embryonic Patterning. PLoS ONE 2(10): e1031.
The Molecular Evolution of Hedgehog in Stolidobranchia Ascidians
Ascidians are highly studied in evolution and development because they have a tiny chordate tadpole larva. As a sister clade to vertebrates, ascidian research has lead to greater understanding of the molecular roles of developmental genes in vertebrates. However, recent research on a Phlebobranchia ascidian Ciona intestinalis indicates that the developmental gene hedgehog (hh) may have undergone a duplication independent to the hh duplications in vertebrates (Hudson, et al. 2011). To investigate this hypothesis, more research is needed on the other ascidian clade, Stolibranchia. In this study we strived to use maximum-likelihood analysis to compare the evolution of hh in Stolidobranchia and Phleobranchia ascidians. Future research will investigate the different developmental roles of hh in Stolidobranchia and Phlebobranchia ascidians. Introduction The members of the chordate phylum-ascidians, cephalochordates, and vertebrates-share specific homologous structures including; the notochord, dorsal nerve cord, pharyngeal gill slits, and post-anal tail (Figure 1). Ascidians have a simplified chordate body plan, and thus many researchers have focused their work on characterizing ascidian development in order to better understand chordate evolution (Imai and Meinertzhagen 2007; Brown et al. 2008). Ascidian development is important for understanding chordate evolution and conserved chordate developmental signaling pathways (Lemaire 2009). The tadpole larvae of ascidians have a body plan surprisingly similar to that of vertebrate embryos, which suggests a degree of conservation in the developmental mechanisms used to generate this body plan (Hudson et al. 2011). Approximately 3000 cells constitute the ascidian tadpole larva, which form many distinct tissues including: the dorsal central nervous system, notochord, muscle, epidermis, mesenchyme, and endoderm (Figure 1) (Takatori et al. 2002). Molecular analysis of solitary ascidian embryogenesis has created a blueprint for the patterning of chordate tissues, which is highly conserved between ascidians and vertebrates (Davidson et al. 2003). Ascidians can be subdivided into three clades: Thaliacea, Phlebobranchia, and Stolidobranchia; in which the latter two contain the majority of ascidians (Zeng, et al. 2006). The major differences in development being that in Stolidobranchia the branchial sac itself is folded, and the regenerative tissue is ectodermal (Kott 1985). Differences in the development of their nervous system are unknown Studies in evolutionary developmental biology have uncovered a 'toolkit' of developmental genes that perform similar functions in various animals (Satou et al. 2009). One of these genes, hedgehog (hh), was discovered to affect segment number and polarity in the fruit fly Drosophila melanogaster (Nüsslein-Volhard and Wieschaus 1980). Mammals have three hh homologs that play important roles in development: Sonic hedgehog (Shh), Indian hedgehog (Ihh) and Desert hedgehog (Dhh) (Takatori et al. 2002). Hh proteins are autocatalyticly cleaved and function as morphogenesis, signals that elicit concentration-dependent responses from target cells (Takatori et al. 2002, Satou 2009). In vertebrate embryos, Shh protein expression is concentrated to the underlying notochord, the ventral midline of the neural tube, and the floor plate (Hudson et al. 2011). Additionally, Shh signals emanating from the notochord and floor plate induce the formation of somatic motor neurons in ventrolateral regions of the neural tube (Takatori et al. 2002, Hudson et al. 2011). Hh signaling has an essential role in humans to
The compact genome of the spongeOopsacas minuta(Hexactinellida) is lacking key metazoan core genes
ABSTRACTBackgroundBilaterian animals today represent 99% of animal biodiversity. Elucidating how bilaterian hallmarks emerged is a central question of animal evo-devo and evolutionary genomics. Studies of non-bilaterian genomes have suggested that the ancestral animal already possessed a diversified developmental toolkit, including some pathways required for bilaterian body plans. Comparing genomes within the early branching metazoan Porifera phylum is key to identify which changes and innovations contributed to the successful transition towards bilaterians.ResultsHere, we report the first whole genome comprehensive analysis of a glass sponge,Oopsacas minuta, a member of theHexactinellida. Studying this class of sponge is evolutionary relevant because it differs from the three otherPoriferaclasses in terms of development, tissue organization, ecology and physiology. AlthoughO. minutadoes not exhibit drastic body simplifications, its genome is among the smallest animal genomes sequen...
The mode of Hedgehog binding to Ihog homologues is not conserved across different phyla
Nature, 2008
Hedgehog (Hh) proteins specify tissue pattern in metazoan embryos by forming gradients that emanate from discrete sites of expression and elicit concentration-dependent cellular differentiation or proliferation responses1 , 2. Cellular responses to Hh and the movement of Hh through tissues are both precisely regulated, and abnormal Hh signaling has been implicated in human birth defects and cancer3 -7. Hh signaling is mediated by its N-terminal domain (HhN), which is dually lipidated and secreted as part of a multivalent lipoprotein particle8 -10. Reception of the HhN signal is modulated by several cell-surface proteins on responding cells, including Patched (Ptc), Smoothened (Smo), Ihog/CDO and the vertebrate-specific proteins Hip and Gas111. Drosophila Ihog and its vertebrate homologs CDO and BOC contain multiple immunoglobulin (Ig) and fibronectin type III (FNIII) repeats, and the first FNIII repeat of Ihog binds Drosophila HhN in a heparin-dependent manner12 , 13. Surprisingly, pull-down experiments suggest that mammalian Sonic hedgehog (ShhN) binds a nonorthologous FNIII repeat of CDO12 , 14. We report here biochemical, biophysical, and X-ray structural studies of a complex between ShhN and the third FNIII repeat of CDO. We show that the ShhN-CDO interaction is completely unlike the HhN-Ihog interaction and requires calcium, which binds at a previously undetected site on ShhN. This site is conserved in nearly all Hh proteins and is a hot spot for mediating interactions between ShhN and CDO, Ptc, Hip, and Gas1. Mutations in vertebrate Hh proteins causing holoprosencephaly and brachydactyly type A1 map to this calcium-binding site and disrupt interactions with these partners.
Mechanisms and functions of Hedgehog signalling across the metazoa
Nature Reviews Genetics, 2011
| Hedgehog proteins constitute one of a small number of families of secreted signals that have a central role in the development of metazoans. Genetic analyses in flies, fish and mice have uncovered the major components of the pathway that transduces Hedgehog signals, and recent genome sequence projects have provided clues about its evolutionary origins. In this Review we provide an updated overview of the mechanisms and functions of this signalling pathway, highlighting the conserved and divergent features of the pathway, as well as some of the common themes in its deployment that have emerged from recent studies.
Molecular biology and evolution, 2014
Sponges (Porifera) are among the earliest evolving metazoans. Their filter-feeding body plan based on choanocyte chambers organized into a complex aquiferous system is so unique among metazoans that it either reflects an early divergence from other animals prior to the evolution of features such as muscles and nerves, or that sponges lost these characters. Analyses of the Amphimedon and Oscarella genomes support this view of uniqueness-many key metazoan genes are absent in these sponges-but whether this is generally true of other sponges remains unknown. We studied the transcriptomes of eight sponge species in four classes (Hexactinellida, Demospongiae, Homoscleromorpha, and Calcarea) specifically seeking genes and pathways considered to be involved in animal complexity. For reference, we also sought these genes in transcriptomes and genomes of three unicellular opisthokonts, two sponges (A. queenslandica and O. carmela), and two bilaterian taxa. Our analyses showed that all sponge ...