Biomedical subjects

Valérie Ledent

Publications and source records attributed to Valérie Ledent.

6 recordsLinked to original sources

PubMed2006

The expression of a hunchback ortholog in the polychaete annelid Platynereis dumerilii suggests an ancestral role in mesoderm development and neurogenesis.

Orthologs of the Drosophila gap gene hunchback have been isolated so far only in protostomes. Phylogenetic analysis of recently available genomic data allowed us to confirm that hunchback genes are widely found in protostomes (both lophotrochozoans and ecdysozoans). In contrast, no unequivocal hunchback gene can be found in the genomes of deuterostomes and non-bilaterians. We cloned hunchback in the marine polychaete annelid Platynereis dumerilii and analysed its expression during development. In this species, hunchback displays an expression pattern indicative of a role in mesoderm formation and neurogenesis, and similar to the expression found for hunchback genes in arthropods. These data suggest altogether that these functions are ancestral to protostomes.

Amino Acid Sequence↗

PubMed2006

Comparative genomics of the class 4 histone deacetylase family indicates a complex evolutionary history.

BACKGROUND: Histone deacetylases are enzymes that modify core histones and play key roles in transcriptional regulation, chromatin assembly, DNA repair, and recombination in eukaryotes. Three types of related histone deacetylases (classes 1, 2, and 4) are widely found in eukaryotes, and structurally related proteins have also been found in some prokaryotes. Here we focus on the evolutionary history of the class 4 histone deacetylase family. RESULTS: Through sequence similarity searches against sequenced genomes and expressed sequence tag data, we identified members of the class 4 histone deacetylase family in 45 eukaryotic and 37 eubacterial species representative of very distant evolutionary lineages. Multiple phylogenetic analyses indicate that the phylogeny of these proteins is, in many respects, at odds with the phylogeny of the species in which they are found. In addition, the eukaryotic members of the class 4 histone deacetylase family clearly display an anomalous phyletic distribution. CONCLUSION: The unexpected phylogenetic relationships within the class 4 histone deacetylase family and the anomalous phyletic distribution of these proteins within eukaryotes might be explained by two mechanisms: ancient gene duplication followed by differential gene losses and/or horizontal gene transfer. We discuss both possibilities in this report, and suggest that the evolutionary history of the class 4 histone deacetylase family may have been shaped by horizontal gene transfers.

Animals↗

PubMed2004

K+ channel interactions detected by a genetic system optimized for systematic studies of membrane protein interactions.

Organization of proteins into complexes is crucial for many cellular functions. However, most proteomic approaches primarily detect protein interactions for soluble proteins but are less suitable for membrane-associated complexes. Here we describe a mating-based split ubiquitin system (mbSUS) for systematic identification of interactions between membrane proteins as well as between membrane and soluble proteins. mbSUS allows in vivo cloning of PCR products into a vector set, detection of interactions via mating, regulated expression of baits, and improved selection of interacting proteins. Cloning is simplified by introduction of lambda attachment sites for GATEWAY. Homo- and heteromeric interactions between Arabidopsis K(+) channels KAT1, AKT1, and AKT2 were identified. Tests with deletion mutants demonstrate that the C terminus of KAT1 and AKT1 is necessary for physical assembly of complexes. Screening of a sorted collection of 84 plant proteins with K(+) channels as bait revealed differences in oligomerization between KAT1, AKT1, and AtKC1, and allowed detection of putative interacting partners of KAT1 and AtKC1. These results show that mbSUS is suited for systematic analysis of membrane protein interactions.

Arabidopsis↗

PubMed2004

Phylogeny of efflux-mediated tetracycline resistance genes and related proteins revisited.

A SRS search in the GenBank/EMBL databases for entire genes encoding efflux-mediated resistance allocated to a recognized tetracycline determinant revealed the existence of at least 87 genes. DNA-based and protein sequence analyses of representatives from the different efflux-mediated tetracycline determinant groups were performed and allowed us to propose a revision of the current grouping on the basis of our new evolutionary trees. On the other hand, similarity, topology, and hydropathy analyses of some representatives from 12-transmembrane segments (TMS) and 14-TMS proteins lead us to perform meaningful sequence alignments of recognized or putative 12-TMS and 14-TMS proteins truncated to their first 200 amino acids (alpha-domain of the protein). For all aligned truncated proteins, including old and recently discovered tetracycline resistance determinants, significant similarities along this segment were demonstrated and three new conserved motifs identified, reinforcing the hypothesis of a common ancestry for the alpha-domain of all tetracycline-efflux pumps.

Algorithms↗

PubMed2002

Phylogenetic analysis of the human basic helix-loop-helix proteins.

BACKGROUND: The basic helix-loop-helix (bHLH) proteins are a large and complex multigene family of transcription factors with important roles in animal development, including that of fruitflies, nematodes and vertebrates. The identification of orthologous relationships among the bHLH genes from these widely divergent taxa allows reconstruction of the putative complement of bHLH genes present in the genome of their last common ancestor. RESULTS: We identified 39 different bHLH genes in the worm Caenorhabditis elegans, 58 in the fly Drosophila melanogaster and 125 in human (Homo sapiens). We defined 44 orthologous families that include most of these bHLH genes. Of these, 43 include both human and fly and/or worm genes, indicating that genes from these families were already present in the last common ancestor of worm, fly and human. Only two families contain both yeast and animal genes, and no family contains both plant and animal bHLH genes. We suggest that the diversification of bHLH genes is directly linked to the acquisition of multicellularity, and that important diversification of the bHLH repertoire occurred independently in animals and plants. CONCLUSIONS: As the last common ancestor of worm, fly and human is also that of all bilaterian animals, our analysis indicates that this ancient ancestor must have possessed at least 43 different types of bHLH, highlighting its genomic complexity.

Animals↗

PubMed2002

Postembryonic development of the posterior lateral line in zebrafish.

We examine how the posterior lateral line of the zebrafish grows and evolves from the simple midbody line present at the end of embryogenesis into the complex adult pattern. Our results suggest that secondary neuromasts do not form through budding from the embryonic line, but rather new waves of neuromasts are added anteroposteriorly. We propose that the developmental module that builds the embryonic pattern of neuromasts is used repeatedly during postembryonic development and that additional (secondary) primordia generate the additional neuromasts. We show that differentiated neuromasts migrate ventrally, and eventually generate "stitches" by successive bisections. We also examine the repatterning of the terminal neuromasts, which anticipates the up-bending of the tail leading to the highly asymmetrical caudal fin of the adult (which develops exclusively from the ventral part of the tail). Because terminal repatterning affects all aspects of tail formation, including its sensory development, we speculate that terminal axis bending may have become intimately associated with the terminal Hox genes before the appearance of the tetrapod lineage.

Animals↗