Evolution & development of skeleton

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

The recruitment, more than 460 million years (Ma) ago, of a mineralized skeleton was a crucial innovation that provided teeth, bones, and various skeletal elements. The well-mineralized tissues (enamel, dentin, bone) of these organs display an overall evolutionary stability of their structure, and thus of their underlying cellular and molecular mechanisms. This means that the specialized cells, the specific proteins of their matrix, and the type of mineral were recruited early in the vertebrate story and have not changed drastically for more than 460 Ma. However, each of these tissues displays a large structural diversity in living species. These last years we have revealed the existence of a continuum between the mineralized tissues (dentin/bone and dentin/enamel) and allowed a better understanding of the origin of the tissue diversity observed in living species.

Today we are interested in the origin, evolution and function of a family of non collagenous proteins involved in the formation and mineralization of these tissues: the secretory calcium-binding phosphoproteins, or SCPPs. Which SCPPs were first present in early vertebrates? How have they evolved? Which role have they played in tissue organization and structure? Do they have the same function in all vertebrate lineages? These are some of the questions we are trying to answer 


  • 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 

  • 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, 
  • study in an evo-devo perspective amelogenesis in model species representative of all vertebrate lineages, 
  • reveal enamel matrix protein gene expression during the formation of the osteoderms in lizards, and 
  • 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.
  • 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".

Future directions

Our expertise in comparative development of teeth (fish, amphibians and reptiles) along with the large amount of data available from studies on the mouse 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.


  • Amelogenesis Imperfecta

Financial support: Hôpitaux de Strasbourg.

Collaboration: Prof A. Bloch-Zupan (Univ. Strasbourg)

  • Title: Towards the origins of vertebrate mineralization: the contribution of large-scale transcriptome sequencing.

Financial support: ANR

Collaboration: Drs F. Delsuc & M. Debiais Thiebaut (ISEM, Univ. Montpellier2); Dr E. Corre (ABIMS, Roscoff)

  • Title: Understanding axial skeleton anomalies in reared sturgeons

Financial support: CIFRE and "Sturio SCEA"


  • 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.


  • 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