|Video: presentation of research topics developped by the team of V. Laudet (in french)|
In the Molecular Zoology group we are fascinated by the diversity of animal life that we study from a developmental, molecular and evolutionary point of view using the new possibilities offered by genomics and molecular genetics. Historically, molecular and cellular biology techniques were used to understand the molecular and genetic basis of life from a small number of model species. More recently, new methodological approaches have expanded our analysis to a wide diversity of other species that can be compared to the model species. In addition, since we now have the complete genome sequences of many animal species, we can shift from the level of the gene to the level of the whole genome. Not only has this changed our view of complex biological processes but also adds to our descriptive knowledge of biodiversity a more functional understanding of this diversity. The name of the team, "Molecular Zoology" underlines the association of two scientific approaches that are too often kept separate: zoology, and molecular and cellular biology.
More specifically, our research fits in two emerging areas: Evo/Devo and genomics of adaptations. Evo/Devo seeks in particular to understand how changes in development led to novelties during evolution, whereas the genomics of adaptations focuses on the modifications that occurred in the genome during these innovations. The main questions that unify our work are therefore evolutionary: What are the genomic bases of evolution? What are the genes that are modified during specific adaptations and species divergence? To tackle such questions we focus our research on taxonomic groups that exhibit a large diversity (in order to have traceable specific adaptations) and which are adapted to the laboratory and experimental research. For these reasons, we mainly focus on two large groups of organisms: the rodents and cypriniform fish, which are extremely diverse (approx. 3000 species each) and provide good laboratory models (the mouse, Mus musculus and the zebrafish Danio rerio).
We also work with the amphioxus (Branchiostoma lanceolatum), a cephalochordate, the most convenient non-vertebrate chordate for inferring what could have been the common vertebrate ancestor.
We explore two very different research avenues, providing us with different perspectives towards understanding the evolution and development of animals and the mechanisms underlying their fascinating diversity. Both strategies are complementary, the starting point of the first one starting “from the organ” level and moving toward genetic and developmental mechanisms, and the second one ranging “from the genes” level to phenotypes. Collectively, our approaches gather information on gene function as well as organ evolution and development and is representative of the general background of our team: a group of molecular biologists asking evolutionary questions in a strong developmental context.
1) "From the organ": Teeth Evo/Devo.
Teeth, a highly mineralized tissue in vertebrates, have an incredible variety of shapes, number, position and size. We try to understand what the important genes for establishing the shape and number of teeth in vertebrates are and which genes were recruited during changes in shape or number. For this we use two types of vertebrates models, rodents and cypriniform fish.
Sophie Pantalacci and Marie Sémon tackle questions on the evolution of tooth morphology at the crossroads of developmental biology and genomics. They notably study the parallel acquisition of two additional cusps on the upper molar in mouse and spiny mouse. They aim at comparing the development of these teeth by a time-series comparative transcriptomic analysis involving these two species and two control-species retaining the ancestral cusp number: gerbil and hamster. They ask whether a convergent morphology implies convergent development, e.g. with some or several genes showing evidence of convergence in their expression profiles. In collaboration with Sabrina Renaud (LBBE, Lyon), they also study a case of parallel evolution of molar morphology in insular mice.
Anne Lambert is associated to the developmental work performed on rodent teeth and is an expert in dissecting tooth buds, performing whole mount in situ hybridization and histological analysis.
Alexa Sadier studies epithelial appendages such as teeth, hairs, claws but also mammary glands, which are adaptive hotspots. She studies the Ectodysplasin (EDA) pathway, which provides a unique window for Evo/Devo studies as it is involved in the development of these appendages. She focuses on the intracellular adaptor of this pathway, EDARADD, which exhibits an interesting variability within mammals. Her results highlight the importance of the fine-tuning of developmental pathways that provides material for subtle variations during evolution.
Marie Tohmé analyses the expression and function of the genes of the EDA pathway in fishes, comparing zebrafish that only have pharyngeal teeth with medaka that contains both oral and pharyngeal teeth. Her results highlight the differential deployment of the genes of this pathway in various species of teleost fishes.
Eric Samarut, in collaboration with Emmanuel Pasco-Viel from Laurent Viriot’s group, as well as with Yann Gibert at Deakin University, explores the diversity of pharyngeal teeth patterns in Cypriniformes and the role that retinoic acid and its receptors played in establishing the tremendous diversity of tooth shape and organization in Cypriniformes.
2) "From the genes": Nuclear receptors. These receptors are ligand-dependant transcription factors that regulate target genes, and thus control specific gene regulatory networks, in response to the binding of their ligand. They form a large family including receptors for very important ligands such as thyroid hormones, estrogens or androgens but also retinoic acid, fatty acids or bile acids. Finally, this family also includes receptors called "orphans" for which no ligand is known and can lead to discovering new active molecules. We have been interested for a long time in the evolution of this family and have traced its origins and diversification back to the early diversification of multicellular animals. We now focus on the precise role of these receptors in the evolution of organisms, using molecular evolution and experimental approaches in zebrafish and amphioxus. Our current view that NR signalling evolves from mechanisms implicated in detoxification led us to explore the interactions between endocrine disruptors and nuclear receptors.
François Bonneton studies the ecdysone receptor, a heterodimer composed of the nuclear receptors ECR and USP. This receptor was maintained in insects despite a dramatic divergence that occurred during the emergence of Mecopterida (the group containing dipteras and lepidopteras among others). Using molecular evolution tools, he studies the constraints acting on this receptor during evolution, how they changed and how they relate to the activities of the receptor (ligand binding, dimerization).
Bachar Chaieb questions the origins of nuclear receptors using bioinformatics and comparative genomic analysis. He is particularly interested in the origin of ligand binding abilities.
Guillaume Holzer explores the evolution of thyroid hormones in metazoans, characterizing this pathway in Protostomes such as Platynereis in collaboration with the Detlev Arendt lab but also in vertebrates that exhibit divergent post-embryonic development strategies such as shark (with Sylvie Mazan’s lab) or platyfish (with Jean-Nicolas Volff’s group).
Claire Lecroisey-Leroy is studying a fascinating case of lineage-specific expansion of gene number in amphioxus. Indeed the amphioxus genome contains 10 copies of FXR, a nuclear receptor known to be a bile acid receptor in human. In collaboration with Hector Escriva in Banyuls and Matthew Krasowski in Iowa, she characterizes the activities of these 10 copies, trying to understand how they have diverged functionally and why they have been maintained. She also charcaterizes NR7, a new nuclear receptor absent in model organisms. She also collaborates with the Dino Moras lab in Illkirch that studies the 3D structure of these receptors.
In collaboration with Michael Schubert in Villefranche, Juliana Guttierez-Mazariegos studies the origins of the retinoic acid pathway in metazoans, characterizing the ligand binding ability of retinoic acid receptor (RAR) homologues in Protostomes. She studies in particular RAR and retinoic acid response in Platynereis with the Detlev Arendt lab. She is also interested in the origins of steroid hormones.
In collaboration with Cecile Egly at IGBMC, Illkirch, Eric Samarut explores the role of phosphorylation of retinoic acid receptors (RARs) in vivo using zebrafish as a model system. This allows him to question the evolution of post-translational modifications in RARs and he discovered that vertebrate RARs can use different regulatory logics to regulate target gene expression and thus perform their biological function.
Liubov Berekelya explores the transcriptional targets of retinoic acid receptors (RAR) in zebrafish with a particular emphasis on DNA methyl transferases that play an important role in controlling the methylation status of DNA, hence the activity of regulatory regions.
Cyril Gaudin is studying the function of RAR (retinoic acid receptor) and ER (estrogen receptor) in zebrafish and how they mediate the action of endocrine disruptors. For this he uses the zinc finger nuclease technology as well as other methods to disrupt gene function in vivo.
Marie Tohmé is working on endocrine disruptors in zebrafish and medaka. She develops transgenic reporter lines and focuses on the action of bisphenol A on the otic vesicle, more specifically on otolith development in collaboration with Yann Gibert of Deakin University in Australia.
In collaboration with Xiaoyong Chenin ECNU, Shangai, China, Ling Li characterizes the effects of Chinese medicine compounds using zebrafish as a model system. She particularly uses GFP reporter lines to study the effects of these compounds in specific organs.
Laure Bernard characterizes the effect of endocrine disruptors on fat metabolism using zebrafish. She is also the surrogate mother to all our fish and makes every fin possible.