Publications

The histone chaperone Asf1 assists in chromatin assembly and remodeling during replication, transcription activation, and gene silencing. However, it has been unclear to what extent Asf1 could be targeted to specific loci via interactions with sequence-specific DNA-binding proteins. Here, we show that Asf1 contributes to the repression of Notch target genes, as depletion of Asf1 in cells by RNAi causes derepression of the E(spl) Notch-inducible genes. Conversely, overexpression of Asf1 in vivo results in decreased expression of target genes and produces phenotypes that are strongly modified (enhanced and suppressed) by mutations affecting the Notch pathway, but not by mutations in other signaling pathways. Asf1 can be coprecipitated with the DNA-binding protein Su(H) and the corepressor Hairless and interacts directly with two components of this complex, Hairless and SKIP. Thus, in addition to playing more general roles in chromatin dynamics, Asf1 is directed via interactions with sequence-specific complexes to mediate silencing of specific target genes.

Two species of Monopylidium Fuhrmann, 1899 are redescribed on the basis of specimens from their type-hosts: M. exiguum (Dujardin, 1845) from Troglodytes troglodytes L. (Passeriformes: Troglodytidae) on the Curonian Spit, Kaliningradskaya Oblast', Russia, and M. albani (Mettrick, 1958) n. comb. (originally Paricterotaenia albani Mettrick, 1958) from Sturnus vulgaris L. (Passeriformes: Sturnidae) in the Canton of Jura, Switzerland. In contrast to the previously proposed synonymy of these two species (Spasskaya & Spasskii, 1977), they are recognised as distinct and M. albani is revalidated.

In eukaryotes, enhancers must often exert their effect over many tens of kilobases of DNA with a choice between many different promoters. Given this situation, elements known as chromatin boundaries have evolved to prevent adventitious interactions between enhancers and promoters. The amenability of Drosophila to molecular genetics has been crucial to the discovery and analysis of these elements. Since these elements are involved in such diverse processes and show little or no sequence similarity between them, no single molecular mechanism has been identified that accounts for their activity. However, over the past approximately 5 years, evidence has accumulated suggesting that boundaries probably function through the formation of long-distance chromatin loops. These loops have been proposed to play a crucial role in both controlling enhancer-promoter interactions and packing DNA.

A species of ichthyodectiform fish, Cladocyclus pankowskii sp.nov. is described based on a single well-preserved braincase specimen from the Cenomanian Kem Kem beds of southern Morocco. It differs from the type species, C. gardneri, in the proportions of the skull roof. The presence of a species of Cladocyclus in Morocco adds yet another vicariant taxon shared between Brazil and Africa in the mid-Cretaceous, when Africa was separating from South America during the formation of the South Atlantic.

Resolving the phylogenetic relationships between eukaryotes is an ongoing challenge of evolutionary biology. In recent years, the accumulation of molecular data led to a new evolutionary understanding, in which all eukaryotic diversity has been classified into five or six supergroups. Yet, the composition of these large assemblages and their relationships remain controversial.

Despite its often featureless appearance, the deep-ocean floor includes some of the most diverse habitats on Earth. However, the accurate assessment of global deep-sea diversity is impeded by a paucity of data on the geographical ranges of bottom-dwelling species, particularly at the genetic level. Here, we present molecular evidence for exceptionally wide distribution of benthic foraminifera, which constitute the major part of deep-sea meiofauna. Our analyses of nuclear ribosomal RNA genes revealed high genetic similarity between Arctic and Antarctic populations of three common deep-sea foraminiferal species (Epistominella exigua, Cibicides wuellerstorfi and Oridorsalis umbonatus), separated by distances of up to 17, 000 km. Our results contrast with the substantial level of cryptic diversity usually revealed by molecular studies, of shallow-water benthic and planktonic marine organisms. The very broad ranges of the deep-sea foraminifera that we examined support the hypothesis of global distribution of small eukaryotes and suggest that deep-sea biodiversity may be more modest at global scales than present estimates suggest.

Genes belonging to both HoxA and HoxD clusters are required for proper vertebrate limb development. Mice lacking all, or parts of, Hoxa and Hoxd functions in forelimbs, as well as mice with a gain of function of these genes in the early limb bud, have helped us to understand functional and regulatory issues associated with these genes, such that, for example, the tight mechanistic interdependency that exists between the production of the limb and its anterior to posterior (AP) polarity. Our studies suggest that the evolutionary recruitment of Hox gene function into growing appendages was crucial to implement hedgehog signalling, subsequently leading to the distal extension of tetrapod appendages, with an already built-in AP polarity. We propose that this process results from the evolutionary co-option, in the developing limbs, of a particular regulatory mechanism (collinearity), which is necessary to pattern the developing trunk. This major regulatory constraint imposed a polarity to our limbs as the most parsimonious solution to grow appendages.

The largest mammalian gene family codes for odorant receptors and is exclusively devoted to the perception of the outside world. Its expression is very peculiar, since olfactory sensory neurons are only allowed to express a single of its numerous members, from a single parental allele. How this is achieved is unknown, but recent work points to multiple regulatory mechanisms, possibly shared by pheromone receptor genes, acting at (a) a general level, via the expression of the chemoreceptor itself and (b) a more restricted level, defined by activator elements.

The potential role of Hox genes during vertebrate limb development was brought into focus by gene expression analyses in mice (P Dolle, JC Izpisua-Belmonte, H Falkenstein, A Renucci, D Duboule, Nature 1989, 342:767-772), at a time when limb growth and patterning were thought to depend upon two distinct and rather independent systems of coordinates; one for the anterior-to-posterior axis and the other for the proximal-to-distal axis (see D Duboule, P Dolle, EMBO J 1989, 8:1497-1505). Over the past years, the function and regulation of these genes have been addressed using both gain-of-function and loss-of-function approaches in chick and mice. The use of multiple mutations either in cis-configuration in trans-configuration or in cis/trans configurations, has confirmed that Hox genes are essential for proper limb development, where they participate in both the growth and organization of the structures. Even though their molecular mechanisms of action remain somewhat elusive, the results of these extensive genetic analyses confirm that, during the development of the limbs, the various axes cannot be considered in isolation from each other and that a more holistic view of limb development should prevail over a simple cartesian, chess grid-like approach of these complex structures. With this in mind, the functional input of Hox genes during limb growth and development can now be re-assessed.

The recent establishment of gene silencing through RNA interference upon feeding opens avenues to decipher the genetic control of regeneration in hydra. Following that approach, we identified three main stages for head regeneration. Immediately post-amputation, the serine protease inhibitor Kazal1 gene produced by the gland cells prevents from an excessive autophagy in regenerating tips. This cytoprotective function, or self-preservation, is similar to that played by Kazal-type proteins in the mammalian exocrine pancreas, in homeostatic or post-injury conditions, likely reflecting an evolutionarily conserved mechanism linking cell survival to tissue repair. Indeed, in wild-type hydra, within the first hours following mid-gastric section, an extensive cellular remodelling is taking place, including phenotypic cellular transitions and cell proliferation. The activation of the MAPK pathway, which leads to the RSK-dependent CREB phosphorylation, is required for these early cellular events. Later, at the early-late stage, the expression of the Gsx/cnox-2 ParaHox gene in proliferating apical neuronal progenitors is required for the de novo neurogenesis that precedes the emergence of the tentacle rudiments. Hence, head regeneration in wild-type hydra relies on spatially restricted and timely orchestrated cellular modifications, which display similarities with those reported during vertebrate epimorphic regeneration. These results suggest some conservation across evolution of the mechanisms driving the post-amputation reactivation of developmental programs.