Biomedical subjects

Thomas C G Bosch

Publications and source records attributed to Thomas C G Bosch.

At least 19 recordsLinked to original sources

PubMed2006

Self/nonself discrimination at the basis of chordate evolution: limits on molecular conservation.

All organisms rely on their capacity of self/nonself discrimination to rapidly detect approaching allogeneic cells as well as invading pathogenic microbes as foreign and to eliminate them. Failure to recognize nonself causes self-mating, germline parasitism and disease. Recent findings indicate that, in urochordates - the closest living relatives of vertebrates - different species use completely different molecules for allorecognition. Thanks to their phylogenetic position, these organisms might help us to understand the evolutionary origin of the vertebrate immune system.

Amino Acid Sequence↗

PubMed2006

Molecular phylogenetics in Hydra, a classical model in evolutionary developmental biology.

Among the earliest diverging animal phyla are the Cnidaria. Freshwater polyps of the genus Hydra (Cnidaria, Hydrozoa) have long been of general interest because different species of Hydra reveal fundamental principles that underlie development, differentiation, regeneration and also symbiosis. The phylogenetic relationships among the Hydra species most commonly used in current research are not resolved yet. Here we estimate the phylogenetic relations among eight scientifically important members of the genus Hydra with molecular data from two nuclear (18S rDNA, 28S rDNA) and two mitochondrial (16S rRNA, cytochrome oxidase subunit I (COI)) genes. The phylogenetic trees obtained by maximum parsimony (MP), maximum likelihood (ML) and Bayesian inference (BI) methods were generally compatible with present morphological classification patterns. However, the present analysis also bears on several long-standing questions about Hydra systematics and reveals some characteristics of the phylogenetic relationships of this genus that were unknown so far. It indicates that Hydra viridissima, the only species in Hydra, which contains symbiotic algae, might be considered as the sister group to all other species within this genus. Analyses of both nuclear and mitochondrial sequences support the view that Hydra oligactis and Hydra circumcincta are sisters to all other Hydra species. Unexpectedly, we also find that in contrast to its initial description, the strain used for making transgenic Hydra, Hydra vulgaris (strain AEP) is more closely related to Hydra carnea than to other species of Hydra.

Animals↗

PubMed2006

Allorecognition in urochordates: identification of a highly variable complement receptor-like protein expressed in follicle cells of Ciona.

The evolutionary origin of allorecognition in vertebrates is unknown. Urochordates, being the closest living relatives of vertebrates [Delsuc F, Brinkmann H, Chourrout D, Philippe H]. Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature 2006; 439: 965-8], have efficient mechanisms to prevent both allogeneic fusion and self fertilization. To shed light on allorecognition in urochordates and on the molecules involved in preventing self fertilization, we compared gonadal cDNAs of three genetically unrelated Ciona intestinalis individuals by suppression subtractive hybridisation (SSH). Here, we report the discovery and characterization of a highly polymorphic gene coding for a transmembrane protein with several short consensus repeat domains (SCR/CCP). The protein, termed variable complement receptor-like 1 (vCRL1), is structurally similar to vertebrate complement receptors. However, in contrast to vertebrate complement receptors, vCRL1 shows an unprecedented high degree of amino acid variations among Ciona individuals and is expressed in follicle cells as well as in hemocytes. Based on our data we propose that in the absence of MHC Ciona uses variable components of the complement system as individuality markers.

Amino Acid Sequence↗

PubMed2006

Dickkopf related genes are components of the positional value gradient in Hydra.

Hydra is a classical model organism to understand fundamental developmental biological processes such as regeneration and axis formation. Here, we show that two genes which share some similarity with members of the Dickkopf family of proteins, HyDkk1/2/4-A and HyDkk1/2/4-C, are co-expressed in gland cells and regulated by the positional value gradient. While HyDkk1/2/4-A is expressed throughout the gastric region, HyDkk1/2/4-C has a graded expression pattern with a high level of transcripts just below the tentacle zone and absence of expression in the budding zone. Blocking the activity of GSK-3beta caused a drastic downregulation of HyDkk1/2/4-C expression in the gastric tissue. Experimental reduction of the number of HyDkk1/2/4-C-expressing cells resulted in expansion of the HyWnt expression domain in the hypostome. Thus, similar to Dickkopf proteins in vertebrates, one of the functions of HyDkk1/2/4-C in hydra may be to antagonize Wnt signalling.

Amino Acid Sequence↗

PubMed2006

Transgenic Hydra allow in vivo tracking of individual stem cells during morphogenesis.

Understanding the evolution of development in large part relies on the study of phylogenetically old organisms. Cnidarians, such as Hydra, have become attractive model organisms for these studies. However, despite long-term efforts, stably transgenic animals could not be generated, severely limiting the functional analysis of genes. Here we report the efficient generation of transgenic Hydra lines by embryo microinjection. One of these transgenic lines expressing EGFP revealed remarkably high motility of individual endodermal epithelial cells during morphogenesis. We expect that transgenic Hydra will become important tools to dissect the molecular mechanisms of development at the base of the Metazoan tree.

Animals↗

PubMed2006

Foot differentiation and genomic plasticity in Hydra: lessons from the PPOD gene family.

In Hydra, developmental processes are permanently active to maintain a simple body plan consisting of a two-layered, radially symmetrical tube with two differentiated structures, head and foot. Foot formation is a dynamic process and includes terminal differentiation of gastric epithelial cells into mucous secreting basal disc cells. A well-established marker for this highly specialized cell type is a locally expressed peroxidase (Hoffmeister et al. 1985). Based on the foot-specific peroxidase activity, the gene PPOD1 has been identified (Hoffmeister-Ullerich et al. 2002). Unexpectedly, this approach led to the identification of a second gene, PPOD2, with high sequence similarity to PPOD1 but a strikingly different expression pattern. Here, we characterize PPOD2 in more detail and show that both genes, PPOD1 and PPOD2, are members of a gene family with differential complexity and expression patterns in different Hydra species. At the genomic level, differences in gene number and structure within the PPOD gene family, even among closely related species, support a recently proposed phylogeny of the genus Hydra and point to unexpected genomic plasticity within closely related species of this ancient metazoan taxon.

Animals↗

PubMed2005

Discovery of genes expressed in Hydra embryogenesis.

Hydra's remarkable capacity to regenerate, to proliferate asexually by budding, and to form a pattern de novo from aggregates allows studying complex cellular and molecular processes typical for embryonic development. The underlying assumption is that patterning in adult hydra tissue relies on factors and genes which are active also during early embryogenesis. Previously, we reported that in Hydra the timing of expression of conserved regulatory genes, known to be involved in adult patterning, differs greatly in adults and embryos (Fröbius, A.C., Genikhovich, G., Kürn, U., Anton-Erxleben, F. and Bosch, T.C.G., 2003. Expression of developmental genes during early embryogenesis of Hydra. Dev. Genes Evol. 213, 445-455). Here, we describe an unbiased screening strategy to identify genes that are relevant to Hydra vulgaris embryogenesis. The approach yielded two sets of differentially expressed genes: one set was expressed exclusively or nearly exclusively in the embryos, while the second set was upregulated in embryos in comparison to adult polyps. Many of the genes identified in hydra embryos had no matches in the database. Among the conserved genes upregulated in embryos is the Hydra orthologue of Embryonic Ectoderm Development (HyEED). The expression pattern of HyEED in developing embryos suggests that interstitial stem cells in Hydra originate in the endoderm. Importantly, the observations uncover previously unknown differences in genes expressed by embryos and polyps and indicate that not only the timing of expression of developmental genes but also the genetic context is different in Hydra embryos compared to adults.

Animals↗

PubMed2005

Towards a molecular code for individuality in the absence of MHC: screening for individually variable genes in the urochordate Ciona intestinalis.

Urochordates possess several well described allorecognitions systems, the molecular nature of those is not yet understood. A prerequisite for any self-/nonself discimination system is the presence of a group of highly variable molecules, which should vary between individuals. Using suppression subtractive hybridisation (SSH) we surveyed Ciona intestinalis for individually variable genes. Our search so far identified two genes, ciS7 and ciMETA2, which both display an unexpected high degree of intra- and interindividual variability, code for secreted proteins, and contain multiple domains suitable for protein-protein interactions. The possible role of these molecules in allorecognition is discussed.

Amino Acid Sequence↗

PubMed2005

Symbiotic Hydra express a plant-like peroxidase gene during oogenesis.

Symbiotic associations accompanied by gene exchange between the symbionts form the phylogenetic origin of eukaryotic cells and, therefore, had significant impact on species diversity and evolutionary novelty. Among the phylogenetically oldest metazoan animals known to form symbiotic relationships are the Cnidaria. In the Cnidarian Hydra viridis, symbiotic algae of the genus Chlorella are located in endodermal epithelial cells and impact sexual differentiation. When screening for Hydra viridis genes that are differentially expressed during symbiosis, we found a gene, HvAPX1, coding for a plant-related ascorbate peroxidase. HvAPX1 is expressed exclusively during oogenesis and in contrast to all known ascorbate peroxidase genes in plants does not contain introns. No member of this gene family has previously been identified from a member of the animal kingdom. We discuss the origin of the HvAPX1 gene and propose that it may have been transferred horizontally following an endosymbiotic event early in evolution of the Hydra lineage as an RNA or cDNA intermediate.

Amino Acid Sequence↗

PubMed2004

A Dickkopf- 3-related gene is expressed in differentiating nematocytes in the basal metazoan Hydra.

In vertebrate development the Dickkopf protein family carries out multiple functions and is represented by at least four different genes with distinct biological activities. In invertebrates such as Drosophila and Caenorhabditis, Dickkopf genes have so far not been identified. Here we describe the identification and characterization of a Dickkopf gene with a deduced amino acid sequence closely related to that of chicken Dkk-3 in the basal metazoan Hydra. HyDkk-3 appears to be the only Dickkopf gene in Hydra. The gene is expressed in the gastric region in nematocytes at a late differentiation stage. In silico searches of EST and genome databases indicated the absence of Dkk genes from the protostomes Drosophila and Caenorhabditis, whereas within the deuterostomes, a Dkk-3 gene could be identified in the genome of the urochordate Ciona intestinalis. The results indicate that at an early stage of evolution of multicellularity Dickkopf proteins have already played important roles as developmental signals. They also suggest that vertebrate Dkk-1, 2 and 4 may have originated from a common ancestor gene of Dkk-3.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Control of asymmetric cell divisions: will cnidarians provide an answer?

Cells in the basal metazoan phylum Cnidaria are characterized by remarkable plasticity in their differentiation capacity. The mechanism controlling asymmetric cell divisions is not understood in cnidarians or in any other animal group. PIWI proteins recently have been shown to be involved in maintaining the self-renewal capacity of stem cells in organisms as diverse as ciliates, flies, worms and mammals. Seipel et al.1 find that, in the cnidarian Podocoryne carnea, the Piwi homolog Cniwi is transcriptionally upregulated when the polyp generates buds, which will develop into medusae. Since transdifferentiation of striated muscle cells to smooth muscle cells also activated Cniwi expression, Cniwi appears to play a crucial role in differentiation events. The discovery should facilitate elucidation of the poorly understood factors that control asymmetric cell divisions at the beginning of animal evolution.

Animals↗

PubMed2004

Recognition strategies in the innate immune system of ancestral chordates.

Many components of the innate immune system in vertebrates can be reliably traced to urochordates and successful strategies for the detection and elimination of pathogens are present at that level of animal evolution, but the issue of where and how the adaptive immune system emerged is still obscure. There is a paucity of evidence for a gradual transition from the innate immune system of invertebrates to the recombinatorial immune system of higher vertebrates. None of the classical elements of MHC based transplantation immunity (MHC, TCR) or humoral immunity (Ig) have been found in urochordates or Agnathans. Nevertheless there is abundant evidence for adaptive immune responses in the agnathans. This remarkable paradox raises a number of questions. How do these ancestral chordates discriminate between the constituents of the external world and the constituents of "self"? Are these strategies universal within the animal kingdom and among chordates, or are different strategies used by representatives of the different taxonomic groups? The current state of our knowledge indicates that the immune system of lower chordates is very different from that of cartilaginous fishes. Pure homology hunting for vertebrate-specific immuno-relevant molecules in invertebrates is therefore of limited value. A more promising approach may involve unbiased functional screening methods. To understand better the evolution of adaptive immune systems, more comparative data from jawless vertebrates (lamprey or hagfish) and a representative of Acrania (e.g. Amphioxus) are clearly needed.

Animals↗

PubMed2004

Genome sizes and chromosomes in the basal metazoan Hydra.

Hydras belong to one of the earliest eumetazoan animal groups, but to date very little is known about their genome sizes, gene numbers, and chromosomes. Here we provide genome size estimates and corresponding karyotypes for five Hydra species. Nuclear DNA contents were assessed by slide-based Feulgen microphotometry. Hydra oligactis possesses the largest genome of 1450 Mbp, followed by similar 1 C capacities in H. carnea (1350 Mbp), H. vulgaris (1250 Mpb) and H. circumcincta (1150 Mbp). The smallest genome of 380 Mbp was determined in H. viridissima. While the number of chromosomes is identical in all five Hydra species (2n = 30), the size of the chromosomes is strictly correlated to the size of the genome, with H. viridissima having conspicuously small chromosomes. The taxonomic and evolutionary significance of the C-value and chromosomal size variation in this ancient group of metazoans as well as its impact on genomic organization and forthcoming genome projects are discussed.

Journal Article↗

PubMed2003

Expression of developmental genes during early embryogenesis of Hydra.

Hydra is a classical model to study key features of embryogenesis such as axial patterning and stem cell differentiation. In contrast to other organisms where these mechanisms are active only during embryonic development, in Hydra they can be studied in adults. The underlying assumption is that the machinery governing adult patterning mimics regulatory mechanisms which are also active during early embryogenesis. Whether, however, Hydra embryogenesis is governed by the same mechanisms which are controlling adult patterning, remains to be shown. In this paper, in precisely staged Hydra embryos, we examined the expression pattern of 15 regulatory genes shown previously to play a role in adult patterning and cell differentiation. RT-PCR revealed that most of the genes examined were expressed in rather late embryonic stages. In situ hybridization, nuclear run-on experiments, and staining of nucleolar organizer region-associated proteins indicated that genes expressed in early embryos are transcribed in the engulfed "nurse cells" (endocytes). This is the first direct evidence that endocytes in Hydra not only provide nutrients to the developing oocyte but also produce maternal factors critical for embryogenesis. Our findings are an initial step towards understanding the molecular machinery controlling embryogenesis of a key group of basal metazoans and raise the possibility that in Hydra there are differences in the mechanisms controlling embryogenesis and adult patterning.

Animals↗

PubMed2003

Urochordates and the origin of natural killer cells: identification of a CD94/NKR-P1-related receptor in blood cells of Botryllus.

Transplantation immunity based on the recognition of MHC molecules is well described in vertebrates. Vertebrates, however, do not undergo transplantation reaction naturally. The phylogenetically closest group in which transplantation reactions can occur is the Urochordata. Therefore, these animals occupy a key position for understanding the evolution of the vertebrate immune system. When screening for genes differentially expressed during allorecognition in Botryllus schlosseri, we isolated a gene coding for a type II transmembrane protein with a C-type lectin-binding domain and close similarity to vertebrates CD94 and NKR-P1. Here we show that the gene, BsCD94-1, is differentially regulated during allorecognition and that a subpopulation of blood cells carries the corresponding receptor on its cell surface. Southern blot analysis with DNA from individual colonies and intronless BsCD94-1 probe reveal variation between individuals at the genomic level. CD94 in vertebrates is one of the markers for natural killer cells and binds to MHC class I molecules. Natural killer cells play a major role in recognition and elimination of allogeneic cells. Their evolutionary origin, however, remained unknown. The results presented here indicate that the elaboration of the vertebrate immune system may have its roots in an ancestral population of cells in the urochordate blood.

Amino Acid Sequence↗

PubMed2003

Enhanced antibacterial activity in Hydra polyps lacking nerve cells.

The nervous system evolved within cnidarians. When assessing antibacterial activity in the freshwater polyp Hydra, we observed a strong correlation between the number of neurons present and the antibacterial activity. Tissue lacking neurons had a drastically enhanced antibacterial activity against Gram-positive (Bacillus subtilis) and Gram-negative (E. coli) bacteria compared to control tissue. The results indicate direct and strong neural influences on immunity in the phylogenetically oldest animals having a nervous system.

Animals↗

PubMed2003

Ancient signals: peptides and the interpretation of positional information in ancestral metazoans.

Understanding the 'tool kit' that builds the most fundamental aspects of animal complexity requires data from the basal animals. Among the earliest diverging animal phyla are the Cnidaria which are the first in having a defined body plan including an axis, a nervous system and a tissue layer construction. Here I revise our understanding of patterning mechanism in cnidarians with special emphasis on the nature of positional signals in Hydra as perhaps the best studied model organism within this phylum. I show that (i) peptides play a major role as positional signals and in cell-cell communication; (ii) that intracellular signalling pathways in Hydra leading to activation of target genes are shared with all multicellular animals; (iii) that homeobox genes translate the positional signals; and (iv) that the signals are integrated by a complex genetic regulatory machinery that includes both novel cis regulatory elements as well as taxon specific target genes. On the basis of these results I present a model for the regulatory interactions required for axis formation in Hydra.

Animals↗

PubMed2003

The Hydra viridis/Chlorella symbiosis. Growth and sexual differentiation in polyps without symbionts.

To investigate interactions between the basal metazoan Hydra viridis and its symbiotic Chlorella algae, we generated aposymbiotic hydra lacking algae and compared them to symbiotic ones with regard to growth and sexual differentiation. Under standard feeding conditions aposymbiotic polyps proliferated similarly to symbiotic polyps. Under moderate and low feeding conditions asexual growth was reduced in polyps lacking algae, indicating that the symbionts supply nutrients to their hosts. In addition, the Chlorella symbionts had a strong influence on the sexual reproduction of Hydra viridis: in most cases female gonads were produced only when symbiotic algae were present. Spermatogenesis proceeded similarly in symbiotic and aposymbiotic polyps. Since during oogenesis symbionts are actively transferred from endodermal epithelial cells to the ectodermal oocytes, this oogenesis promoting role could indicate that the symbionts are critically involved in the control of sexual differentiation in green hydra.

Journal Article↗