The general strategy of our team is to ask relevant evolutionary questions and to address these questions through the use of molecular approaches that are available in modern biology. We are exclusively studying animals and the name of the team “molecular zoology” reflect this double interest of being interested both by organism biology and evolution and using molecular genetic, developmental biology and comparative genomics as methods of analysis.
We are studying essentialy two biological objects that are completely different (a gene superfamily encoding nuclear hormone receptors and complex mineralized structures, teeth) but that are in fact connected by several links and that allow to ask a serie of complementary questions, that are receiving strong interest by the scientific community.

Our first scientific object, a superfamily: nuclear hormone receptors

By transducing the message of the classical hormones of endocrinology (steroid hormones, such as estrogens or corticoids, but also thyroid hormones and vitamin D) nuclear receptors (NRs) play essential roles in embryonic development, maintenance of differentiated cellular phenotypes, metabolism, and cell death. Dysfunction of the signaling pathways governed by these ligand-activated transcription factors leads to proliferative, reproductive and metabolic diseases such as cancer, infertility, obesity or diabetes. The NR superfamily contains many liganded receptors (24 among the 48 known NRs in the human genome), but also “orphan” receptors, for which no ligand has yet been discovered. It is unknown whether all orphan receptors have the potential to bind natural or synthetic ligands or if they are “true” orphans that do not possess a bona fide ligand-binding pocket and may be regulated by alternative mechanisms. Undoubtedly, the existence of orphan receptors with apparent (patho-) physiological activities constitutes both a major challenge for NR research and a potential opportunity for drug discovery. The question of the origin of orphan receptors and of their relationships with liganded receptors has become a central one in NR research with new data provided by ongoing genome projects. This question also has very interesting evolutionary implications.
The diversity of the nuclear receptor superfamily was the main aspect that drove our research since the origin of the group in 1995. In fact, studying the evolution of nuclear receptors proved to be an excellent conceptual platform, on which important scientific questions have been developed:

1. Discussing the origin and evolution of NRs is tightly linked to the question of the origin and diversification of major endocrine systems, that are governing the physiology and metabolism of the organism as a whole. The origin of the ligand/receptor couple is a long-standing debate linked to the fundamental question of the origin of complex systems that has not been solved yet.
2. The pattern of NR evolution has important implications for the ongoing discussions around the origin of metazoan as illustrated for example by one major clade of metazoan, the ecdysozoan, that is named in reference to molting, a process directly regulated by a NR ligand, ecdysone.
3. The main steps of NR diversification followed the major trends of genome evolution with genome duplications, lineage specific expansion and gene loss playing major roles. It has proven extremely fruitful to use NRs as a proxy to better understand structurally and functionally the processes shaping genomes across time. We have built over the years a specific interest in genome research and we regularly pass from the scale of the superfamily to the whole genome scale and vice versa.
4. NRs have played a direct and major role in specific events during evolution. In that sense they were actors in the emergence of biodiversity. This is for example the case of the role of thyroid hormones in the regulation of vertebrate metamorphosis. Studying this process using molecular approaches in a broad comparative perspective has led to a redefinition of ancient zoological concepts such as neoteny or even metamorphosis itself.

In summary, our credo is really to tackle the question of evolution of nuclear receptors using the most accurate methodological approaches without considering the traditional limits of biological disciplines and mixing the competences and approaches of the members of the team. Solving major evolutionary questions using molecular and integrated approaches using NRs as a starting point is an original strategy that was really fruitful

Examples of ongoing research projects in this field:
Role of thyroid hormones in the evolution of metamorphosis in chordates.
Identification and evolution of the gene regulatory network controlled by retinoic acid.
Evolution and development of the retinoic acid signalling cascade in chordates.
Evolutionary plasticity of nuclear receptors in the ecdysone pathway of insects.
Effects of endocrine disruptors during zebrafish development
Development of NureXbase a specific database for nuclear receptors.

Our second biological object: vertebrate teeth

One of the most important question in biology is to identify, which genes were recruited in building specific morphoanatomical structures; how this recruitment occurred and how these mechanisms may led to evolutionary changes. We thus selected teeth as a relevant biological structure exhibiting several examples of adaptative morphofunctional changes that are sufficiently well-described to be analyzed at the developmental, molecular and evolutionary levels. Indeed, vertebrate teeth are incredible biological objects that are, without any doubt, direct products of natural selection, since they are crucial for handling and processing food. Teeth indeed offer a very nice substratum for our research and studying these structures in two different vertebrates group, the rodents and the actinopterygian fish, is relevant because of 5 main reasons:

1. In rodents as well as in fish, the size, number, and shape of teeth are evolving fast and experienced an astonishing number of adaptations. Both rodents and fish are highly speciose groups: actinopterygian cluster about 25 000 species, half of all vertebrate species. Similarly, almost half of all current and fossil mammals are in fact rodents. Within the two groups, we find species whose dental features have remained primitive as well as other groups with highly derived patterns.
2. A high number of developmental studies of the laboratory mouse as well as in the zebrafish allow us to understand quite well the basics of tooth development. In all known vertebrates, the tooth develops within a process of epithelium-mesenchyme interactions, first similar to that observed in other organs (limbs, hair, glands), and then specific to the type of tooth studied (incisor or molars in the case of mice). In particular, the Wnt, FGF, BMP Hh pathways play an important role as well as transcription factors, such as Msx1/2 and Pax1/9, all very well-studied genes that are therefore well-known to developmental biologists.
3. Several complete genomes are already available in actinopterygian fish and rodents. For rodents the laboratory mouse and rats but also the guinea pig and squirrel genomes are available and others (e.g. Dipodomys) will come soon. In addition, other mammalian genomes provide valuable outgroups. In actinopterygian fish, in addition to the two pufferfish genomes already sequenced, the genomes from zebrafish, medaka and sticklebacks are also available.
4. The possibility of thorough genetic experimentation exists by using laboratory model organisms, such as the mouse, Mus musculus, and the zebrafish, Danio rerio, as references. In both cases it is possible to experimentally modify gene expression (e.g. using transgenic and homologous recombination in mouse and morpholino or mRNA injection in zebrafish) and thus to directly test our hypotheses. We see this constant exchange between comparative evolutionary work and experimental test using model organisms as an essential strength of this project.
5. An exceptional paleontological documentation: teeth are the body parts that are best preserved during fossilization. They carry very specific characters, thus allowing species to be identified, even when they are closely related. This is of course true for rodents, since the history of the group is mainly a history of their teeth, but this is also true for fish, even if for this group the paleontological record is less complete than that of rodents.

It is important to note that the work done using these two models is in fact tightly connected because: (i) the underlying basic question is the same; (ii) the methods and concepts used to solve these questions are similar; (iii) both can supply interesting results to the other. In addition, bioinformatic analyses will represent the "cement" that will play a major role in linking these two projects.
One can see that the ‘tooth’ model will be very powerful to compare morphological evolution between species and to determine their genetic bases. What are the genes that were selected/modified during these adaptations? What were the expression and/or biochemical functions of these genes? In other words, what were the molecular targets of natural selection during teeth adaptations in rodents and actinopterygian fish? The possibility to involve in this project different approaches including several external collaborations with different skills, technologies and approaches will obviously be an important asset as it will allow us to deploy a really multidisciplinary network to answer these questions.

Examples of ongoing research projects in this field:
Molecular evolution of the EDA pathway in vertebrates
Role of the EDA pathway in rodent teeth evolution
Evolution and development of palatal ridges in rodents
Molecular phylogeny, evolution and adaptations of rodents
Role of retinoic acid in teeth development and evolution in zebrafish
Evolutionary trends governing pharyngeal teeth diversity in Cypriniformes