PubMed Health⌕ Search

Biomedical subjects

Jürg Spring

Publications and source records attributed to Jürg Spring.

9 recordsLinked to original sources

T-box and homeobox genes from the ctenophore Pleurobrachia pileus: comparison of Brachyury, Tbx2/3 and Tlx in basal metazoans and bilaterians.

Most animals are classified as Bilateria and only four phyla are still extant as outgroups, namely Porifera, Placozoa, Cnidaria and Ctenophora. These non-bilaterians were not considered to have a mesoderm and hence mesoderm-specific genes. However, the T-box gene Brachyury could be isolated from sponges, placozoans and cnidarians. Here, we describe the first Brachyury and a Tbx2/3 homologue from a ctenophore. In addition, analysing T-box and homeobox genes under comparable conditions in all four basal phyla lead to the discovery of novel T-box genes in sponges and cnidarians and a Tlx homeobox gene in the ctenophore Pleurobrachia pileus. The conservation of the T-box and the homeobox genes suggest that distinct subfamilies with different roles in bilaterians were already split in non-bilaterians.

Amino Acid Sequence↗

Expression pattern of the homeobox gene Not in the basal metazoan Trichoplax adhaerens.

The homeobox gene Not is highly conserved in Xenopus, chicken and zebrafish with an apparent role in notochord formation, which inspired the name of this distinct subfamily. Interestingly, Not genes are also well conserved in animals without notochord such as sea urchins, Drosophila or even Hydra, but appear to be highly derived in mammals. A search for homeobox genes in the placozoan Trichoplax adhaerens, one of the simplest organisms available today, revealed only two homeobox genes: a Not homologue and the previously described gene Trox-2, which is most similar to the Gsx subfamily of the Hox/ParaHox cluster genes. Not has a unique expression profile in Trichoplax. It is highly expressed in folds of intact animals and in the wounds of regenerating animals. The dynamic expression pattern of Trichoplax Not is discussed in comparison with the invariable expression pattern of Trox-2 and the putative secreted protein Secp1. The high sequence conservation of Not from Trichoplax to lower vertebrates, but not to mammals, represents a rare example of an apparent gene decay in the lineage leading to humans.

Amino Acid Sequence↗

A new membrane-attack complex/perforin (MACPF) domain lethal toxin from the nematocyst venom of the Okinawan sea anemone Actineria villosa.

The Okinawan sea anemone Actineria villosa causes severe cases of stinging. We isolated the 60 kDa A. villosa toxin (AvTX-60A) as the major toxin from the isolated nematocysts of this species. AvTX-60A showed fatal toxicity to mice with intraperitoneal injection at a minimum lethal dose of less than 250 microg/kg. The N-terminal amino acid sequence was determined and the corresponding cDNA encoding AvTX-60A was sequenced. The deduced amino acid sequence of AvTX-60A showed high similarity with PsTX-60A, which had been isolated as one of the major toxins from the venomous sea anemone Phyllodiscus semoni. These sea anemone toxins are new members of the family of proteins containing membrane-attack complex/perforin (MACPF) domains, best known in pore forming proteins such as perforin. These are the first examples of MACPF domain proteins as toxins for prey acquisition or repelling predators in nature.

Amino Acid Sequence↗

Distinct expression patterns of the two T-box homologues Brachyury and Tbx2/3 in the placozoan Trichoplax adhaerens.

Trichoplax adhaerens is the only species known from the phylum Placozoa with one of the simplest metazoan body plans. In the small disc-like organism an upper and a lower epithelium can be distinguished with a less compact third cell layer in between. When Trichoplax was first described in 1883, the relation of these three cell layers with ectoderm, endoderm and mesoderm of higher animals was discussed. Still, little is known about embryonic development of Trichoplax, however, genes thought to be specific for mesoderm in bilaterian animals turned out to be already present in non-bilaterians. Searching for a Brachyury homologue, two members of the T-box gene family were isolated from Trichoplax, Brachyury and a Tbx2/3 homologue. The T-box genes encode a transcription factor family characterized by the DNA-binding T-box domain. T-box genes have been found in all metazoans so far investigated, but in contrast to other transcription factors such as the homeobox family, T-box genes are not present in plants or fungi. The distinct expression patterns of two T-box genes in Trichoplax point to non-redundant functions already present at the beginning of animal evolution. Since the expression patterns derived by in situ hybridization do not overlap with anatomical structures, it can be concluded that this simple animal has more than the four cell types described in the literature. This hidden complexity and the unresolved position in relation to Porifera, Cnidaria, Ctenophora and Bilateria highlight the necessity of the inclusion of Trichoplax in studies of comparative evolutionary and developmental biology.

Amino Acid Sequence↗

Identification of the Drosophila melanogaster homolog of the human spastin gene.

The human SPG4 locus encodes the spastin gene, which is responsible for the most prevalent form of autosomal dominant hereditary spastic paraplegia (AD-HSP), a neurodegenerative disorder. Here we identify the predicted gene product CG5977 as the Drosophila homolog of the human spastin gene, with much higher sequence similarities than any other related AAA domain protein in the fly. Furthermore we report a new potential transmembrane domain in the N-terminus of the two homologous proteins. During embryogenesis, the expression pattern of Drosophila spastin becomes restricted primarily to the central nervous system, in contrast to the ubiquitous expression of the vertebrate spastin genes. Given this nervous system-specific expression, it will be important to determine if Drosophila spastin loss-of-function mutations also lead to neurodegeneration.

Adenosine Triphosphatases↗

Evolutionary aspects of developmentally regulated helix-loop-helix transcription factors in striated muscle of jellyfish.

The function of basic helix-loop-helix (bHLH) proteins in cell differentiation was shown to be conserved from Drosophila to vertebrates, exemplified by the function of MyoD in striated muscle differentiation. In phylogeny striated muscle tissue appears first in jellyfish and the question of its evolutionary position is controversially discussed. For this reason we have studied the developmental role of myogenic bHLH genes in medusa development. Based on their dimerization ability, four genes of the bHLH family of transcription factors were isolated from the hydrozoan jellyfish Podocoryne carnea. While the proteins Id and Ash group with cognate family members from bilaterians, Net-like and JellyD1 could not be unequivocally classified. Id is expressed during the medusa budding process and in the adult medusa, Ash and Net-like are expressed in all life cycle stages from egg to adult medusa and JellyD1 is expressed in the blastula and gastrula stages, the planula larva, and in late medusa bud stages. The dimerization specificity, the expression pattern, and the conservation of two residues specific for a MyoD bHLH domain suggest that JellyD1 is related to an ancestral MyoD gene. Id, Net-like, and JellyD1 are either expressed in the entocodon or its derived tissues, the striated and smooth muscle of the bell. These findings strengthen the hypothesis that the entocodon is a mesoderm-like structure and that the common ancestor of Cnidaria and Bilateria was more complex in cell-type architecture and body organization than commonly thought.

Amino Acid Sequence↗

Major transitions in evolution by genome fusions: from prokaryotes to eukaryotes, metazoans, bilaterians and vertebrates.

The major transitions in human evolution from prokaryotes to eukaryotes, from protozoans to metazoans, from the first animals to bilaterians and finally from a primitive chordate to vertebrates were all accompanied by increases in genome complexity. Rare fusion of divergent genomes rather than continuous single gene duplications could explain these jumps in evolution. The origin of eukaryotes was proposed to be due to a symbiosis of Archaea and Bacteria. Symbiosis is clearly seen as the source for mitochondria. A fundamental difference of higher eukaryotes is the cycle from haploidy to diploidy, a well-regulated genome duplication. Of course, self-fertilization exists, but the potential of sex increases with the difference of the haploid stages, such as the sperm and the egg. What should be the advantage of having two identical copies of a gene? Still, genes duplicate all the time and even genomes duplicate rather often. In plants, polyploidy is well recognized, but seems to be abundant in fungi and even in animals, too. However, hybridization, rather than autopolyploidy, seems to be the potential mechanism for creating something new. The problem with chimaeric, symbiotic or reticulate evolution events is that they blur phylogenetic lineages. Unrecognized paralogous genes or random loss of one of the paralogs in different lineages can lead to false conclusions. Horizontal genome transfer, genome fusion or hybridization might be only truly innovative combined with rare geological transitions such as change to an oxygen atmosphere, snowball Earth events or the Cambrian explosion, but correlates well with the major transitions in evolution.

Animals↗

Conservation of Brachyury, Mef2, and Snail in the myogenic lineage of jellyfish: a connection to the mesoderm of bilateria.

One major difference between simple metazoans such as cnidarians and all the bilaterian animals is thought to involve the invention of mesoderm. The terms diploblasts and triploblasts are therefore, often used to group prebilaterian and bilaterian animals, respectively. However, jellyfish contain well developed striated and smooth muscle tissues that derive from the entocodon, a mesoderm-like tissue formed during medusa development. We investigated the hypothesis, that the entocodon could be homologous to the third germ layer of bilaterians by analyzing the structures and expression patterns of the homologues of Brachyury, Mef2, and Snail in the jellyfish Podocoryne carnea. These are regulatory genes from the T-box, MADS-box and zinc finger families known to play important roles in bilaterian mesoderm patterning and muscle differentiation. The sequence and expression data demonstrate that the genes are structurally and functionally conserved and even more similar to humans or other deuterostomes than to protostome model organisms such as Drosophila or Caenorhabditis elegans. Based on these data we conclude that the common ancestor of the cnidarians and bilaterians not only shared genes that play a role in regulating myogenesis but already used them to develop and differentiate muscle systems similar to those of triploblasts.

Animals↗