Evolution et développement du squelette

La formation, il y a plus de 460 millions d'années (Ma) d'un squelette fut un évènement crucial dans l'évolution des vertébrés. Les tissus (émail, dentine, os) composant aujourd'hui les dents et les autres éléments du squelette étaient déjà présents chez les premiers vertébrés. Cette grande stabilité tissulaire indique que les cellules spécialisées, les protéines matricielles spécifiques, le type de minéral déposé et, de fait, des mécanismes cellulaires et moléculaires sous jacents ont été recrutés très tôt dans l'histoire des vertébrés et n'ont pas été profondément modifiés pendant plus de 460 Ma. Cependant, dans les diverses lignées de vertébrés, ces tissus montrent une grande diversité de structure et d'organisation.

Récemment, nous avons identifié un continuum entre dentine et os et entre dentine et émail et pu comprendre l'origine de la diversité tissulaire et les relations de parenté de la plupart de ces tissus.

Aujourd'hui, nous nous intéressons à l'origine, l'évolution et les fonctions d'une dizaine de protéines impliquées dans la formation et le contrôle de la minéralisation de ces tissus: la famille des phosphoprotéines secrétées liant le calcium, ou SCPPs. Quelles étaient les premières SCPPs? Comment ont-elles évolué et quel rôle ont-elles joué dans la structure des tissus? Ont-elles les mêmes fonctions chez tous les vertébrés? Ce sont quelques unes des questions auxquelles nous tentons de répondre.

En savoir plus...

The activity of EDS Groupis focused on the evolution of the vertebrate skeleton with two main research projects: (1) history of the mineralized skeletal tissues and of the "mineralizing" proteins, and (2) tooth evo-devo.

  • 1- History of the mineralized skeletal tissues and of the mineralizing proteins

Mineralized skeletal tissues (dentin, bone and enamel) were identified with certainty in jawless vertebrates from the early Ordovician, c. 460 millions years ago (Ma). Their characteristics were similar to those in modern vertebrates, which indicates that these tissues display an overall evolutionary stability of their structure, and thus of their underlying cellular and molecular mechanisms. We recently proposed an evolutionary scenario for the mineralized tissues in vertebrates. This study revealed the existence of a continuum between the mineralized tissues (dentin/bone and dentin/enamel) and allowed a better understanding of the origin and relationships of the large tissue diversity observed in living species. Although most of the hypotheses are well supported by developmental and paleontological data some issues remain obscure. It appeared in particular that a better knowledge of the origin and evolution of a particular group of non-collagenous proteins collectively called "secretory calcium-binding phosphoproteins - SCPP" could highlight these issues.

Bone and tooth mineralization is indeed mostly regulated by SCPPs that include enamel, and bone and dentin proteins. SCPP genes arose through successive tandem duplications, the first one probably originating from an ancestral SPARC-like 1 gene. Gene duplication certainly occurred before the first mineralized tissues were identified in early vertebrates. Unfortunately, because the SCPP sequences are not well conserved during evolution (unordered proteins), our knowledge is currently limited to tetrapods in the sarcopterygian lineage and, partially only, to teleosts in the actinopterygian lineage, both having diverged around 450 Ma.

These last years we have performed a number of studies aiming to understand SCPP evolution in mammals (amelogenin, enamelin, amelotin, MEPE, DMP1 and ameloblastin), to highlights conserved residues and domains, and to validate or predict mutation leading to genetic diseases.

Now our research efforts are devoted to (i) enlarge our data set of SCPP sequences by studying all vertebrate lineages (jaw transcriptome project) in order to identify SCPPs that were present at the onset of the mineralized skeletal elements in early vertebrates and were responsible for initiating a new type of mineral based on calcium phosphate instead of calcium carbonate in non vertebrates, (ii) study in an evo-devo perspective amelogenesis in model species representative of all vertebrate lineages, (iii) reveal enamel matrix protein gene expression during the formation of the osteoderms in lizards, and (iv) highlight the genetic mechanisms subjacent to tooth replacement in non mammalian model species (lizards, salamanders, teleost fish). To this aim we use data sets of transcript sequences obtained from the transcriptomes of tooth-containing jaws of the target species.

  • 2- Evo-Devo

For years this group is involved in developmental comparative studies of tooth and tooth-related tissues in non mammalian vertebrates with a particular focus on various species of "fish" (dogfish, zebrafish, several basal lineage species such as polypterids, lepisosteids, sturgeons, lungfish, etc.), amphibians (mainly the salamander Pleurodeles) and reptiles (crocodiles and lizards). These studies were performed mostly in collaboration with European partners, and led to numerous publications concerning the morphogenesis and differentiation of teeth and various types of scales, including scutes and tetrapod osteoderms. Comparative analyses of the development and structure of the large diversity of dermal skeletal tissues in extant and extinct vertebrate species led to an evolutionary scenario that was recently published in J. Anat. (Sire et al., 2009; Vickaryous and Sire, 2009). These studies also revealed a new direction of research concerning the enameloid/enamel transition (i.e., epidermal + dermal participation versus epidermal production alone, respectively) during tooth development and evolution. Currently we are looking for various markers through odontogenesis in a salamander (pleurodeles) bred in our laboratory, a process that could be a remnant of what occurred during evolution of early vertebrates. We plan in the future to move on with in situ experimentations in various "fish".

Our expertise in comparative development of teeth (fish, amphibians and reptiles) along with the large amount of data available from studies on the mouse (Fig. 3) has conducted us to start an extensive study on tooth development in a lizard, the green anole taken as a model species (mostly because of its sequenced genome). In particular, we will focus on tooth replacement with the objective to better understand its genetic basis and to be able to find genes and/or signaling pathways involved in the activation of stem cells that seems to be a prerequisite for initiating tooth replacement. Such a research direction is obviously in a strong connection with the fact that continuous tooth replacement was lost in mammals and with the current idea that tooth replacement could be eventually re-initiated in humans provided an appropriate activation of adult stem cells. A large amount of data is available from studies on hair and feather replacement in mammals and also from studies of the continuously grawing incisors in the mouse providing us with a large range of tools that could be used in our study (Fig. 4).


  • Prof A. Bloch-Zupan (Univ. Strasbourg)
  • Drs F. Delsuc & M. Debiais Thiebaut (ISEM, Univ. Montpellier2); Dr E. Corre (ABIMS, Roscoff)
  • International

- Belgium: Pr. A. Huysseune, Gent Univ.;

- Netherlands: Pr. M. Richarson, Leiden Univ.;

- UK: Dr A. Tucker, Univ. London College;

- Israel: Pr. D. Deutsch, Univ. Jerusalem; Dr J. Silvent, Univ. Tel Aviv;

- Canada: Pr B. Ganss, Univ. Totonto; Dr M. Vickaryous, Univ. Guelph; Dr M-A.Akimenko, Univ. Ottawa; Dr G. VandenBerg & MH Deschamps, Univ. Laval in Quebec; Dr R. Cloutier, Univ. Rimousky

- USA: Pr. Thomas Diekwisch, Univ. Chicago; Dr K. Kawasaki, Univ. Pennsylvania.

  • National

- Paris: Dr V. de Buffrénil, Muséum national d'Histoire naturelle; Pr C. Chaussain, Univ. Paris-Descartes; Dr E. Mornet, Univ. Versailles;

- Strasbourg: Pr A. Bloch-Zupan, Univ. Strasbourg;

- Lyon: Dr A. Louchart, ENS-Lyon;

- Montpellier: Dr F. Delsuc, M. Debiais -Thiebaut, Univ. Montpellier 2

- Perpignan: Dr R. Galzin, EPHE