Objective
A.GENERAL BACKGROUND
Teeth occupy a unique position in biology:
1.Teeth represent an important part of fossil records.
2.The embryonic dentition constitutes a powerful tool and a model for developmental biologists and biologists in a broad sense.
3.Teeth have important implications in public health and results from fundamental research should be turned into practical healthcare.
The European laboratories willing to participate are active in complementary domains including:
-comparative anatomy and molecular biology;
-dental cell specification and patterning;
-tooth histo-morphogenesis and cytodifferentiation;
-cellular and molecular biology of tooth supporting tissues;
-extracellular matrix and biomineralization;
-reparative processes related with caries, dental trauma and periodontitis.
These laboratories are rather small and there is an unequal distribution of European expertise. The COST system should allow the coordination of complementary research activities, to improve efficacy and to avoid unprofitable redundancies. This COST Action, which does not overlap with other European scientific programmes, should also increase and valorize the European potential in the domain of tooth related molecular genetics.
B.OBJECTIVES OF THE ACTION
The main objective of the Action is to increase our knowledge of cellular and molecular aspects of normal and abnormal tooth formation and to make this information profitable for clinical work including prevention, epidemiology, genetic counselling and therapeutics.
The secondary, derived, objectives range from more general, fundamental aspects to well focused specific problems:
-Positive, constructive interaction of developmental biologists, comparative anatomists and paleontologists. Phylogeny and ontogeny have to be reunited around the centrality of heterochrony: An integrated model of odontogenesis should be developed.
-Unravelling the molecular identity of neural crest derived dental cells.
-Resolving the mechanisms of their patterning in the developing jaws.
-Elucidating the nature of epithelial-mesenchymal signalling leading to tooth specific histo-morphogenesis and eruption.
-Further characterization of the phenotypes of dental papilla cells, odontoblasts, ameloblasts, cementoblasts, and the cells of the periodontium.
-Understanding of the control mechanisms involved in specific phenotypic expressions.
These investigations will improve our understanding of inherited and non-inherited abnormalities and dysplasiae and will generate progress in the development of adequate therapies in the frame of reparative dentinogenesis and periodontal disease.
In order to reach these ambitious goals, implying multidisciplinarity, collaboration is required. The important European potential in the field has to be exploited through coordination, rapid exchange of scientific information, and sharing of laboratory facilities and technical expertise. Such an integration will increase our knowledge and will generate economic and social benefits.
C.THE SCIENTIFIC CONTENT (PROGRAMMING) OF THE ACTION
The participating laboratories will interact in the frame of 4 partially overlapping working groups (WG). According to the topics of each WG the members of the participating laboratories will join one or several WGs.
-WG1:"Evolution".
-WG2:"Neural crest cells, patterning, tooth initiation".
-WG3:"Histo-morphogenesis and cytodifferentiation in development and repair".
-WG4:"Extracellular matrix-mineralization".
Common tasks: All participants will provide detailed information concerning their laboratory facilities and their technical expertise. The modalities of access to specific equipment and technologies will be defined: common research teams and/or exchange of researchers, technicians, between laboratories. All of this information will be made available through a data bank.
Specific aims:
WG1:Paleontologists, comparative anatomists and interested developmental biologists will meet and will attempt to understand how homodont dentitions evolved. Cellular and molecular comparisons of odontogenesis in selected fish (including the Zebrafish, an actual model for genetic and molecular investigations), dolphins (available collections exist) rodents, amphibians and humans will be performed.
WG2:Most of our current knowledge concerning the neural crest derives from experiments performed in amphibian and avian embryos. Most of these data suggest that at least some of the neural crest cells are multipotent prior to their migration, yet virtually no data exists concerning the commitment of connective tissue phenotypes including dental cells. Knowing the putative role of Hox genes, homeobox and other regulatory genes, in conferring molecular indentity; and the rule of retinoic acid and vitamin D pathways, as well as the role of growth factors in cell communication and signalling, the interaction of molecular and cell biologists and bringing into play the available molecular technologies (RT-PCR: antisense strategies, transgenic animals, transfections, etc.) will greatly improve our understanding of the initial events of odontogenesis.
WG3:Homotypic and heterotypic cell interactions implying growth factors, substrate adhesion molecules, cell adhesion molecules, cell junction molecules, etc., regulate tooth histo-morphogenesis and cytodifferentiation. Again, collaboration of morphologists, molecular and developmental biologists is required to try to understand how tooth specific morphogenesis is regulated. Computer assisted 3D reconstructions at all stages, implying morphology, the distribution patterns of mitoses, and apoptoses and of specific transcripts and proteins, will represent a powerful tool. Several European laboratories, familiar with such technology, have to be interconnected.
During recent years some significant strides were made concerning the control of terminal differentiation of dental cells. People involved in such research have now to interact with researchers working in the fields of reparative dentinogenesis and periodontitis. Such collaboration should lead to foreseeable progress in the development of specific therapeutics.
WG4:Today no universal theory explains biomineralization. Teeth, including dentin, enamel, cementum and bone of attachment constitute the most powerful model for analyzing these processes in normal and pathological (inherited or non-inherited) conditions. Structural and compositional (analytical) comparisons in vivo as well as induction of mineralization in reduced in vitro systems have to be further investigated. For obvious reasons the molecular mechanisms of fluoride action have to be investigated. It is also of importance to evaluate the risk of anti-cancer therapy on children's dentition. Specialists in complementary domains (proteoglycans, glycosaminoglycans, non collagenous proteins, collagens, enamel proteins, Ca2- channels, specific enzymes...) will interact.
The participants of each WG will initiate specific collaborations - common research teams, exchange of researchers between laboratories - WG meetings will be organized and the WG coordinators will coordinate interactions between the different WGs. International mid-term and final meetings will be organized. The outcome of our research will be published in well reputed international journals. The mid-term and final evaluations should lead to publication of detailed activity reports.
D.TIMETABLE
E.ORGANIZATION MANAGEMENT AND RESPONSIBILITIES
The network involved in the Action consists of four interacting working groups. Four different coordinators, members of the Management Committee, will be appointed by the committee. Each WG coordinator, assisted by a co-opted vice-coordinator, will prepare the initial consensus report to initiate the interactions and collaborations of the WGs. All the members of the WGs accept to inform the coordinator on their progress, on their encountered difficulties and also on possible ongoing national programmes and possible interferences. The coordinators will inform the secretariat of the Management Committee every quarter to allow follow-up of the action.
According to the rules of procedure the Management Committee is convened at least twice a year and particularly
-at the starting point (to appoint the WG coordinators, to initiate the data bank, to define place and dates of the first WG meetings)
-immediately after the meeting of WG4 of phase 2
-in the framework of all the meetings of phases 3 to 6.
Furthermore, each member of the Management Committee (including the WG coordinators) may ask for an extraordinary Management Committee meeting to improve interactions of the WGs, to discuss unexpected problems and to allow countries not participating in the planning to join the Action.
The Management Committee also makes decisions (in the framework of existing general guidelines) concerning the question of intellectual property rights and draws up the annual report.
F.ECONOMIC DIMENSION OF THE ACTION
The overall cost of the activities carried out under the Action has been estimated on the basis of information available during the planning of the Action.
Current status
In order to reach the scientific goals of the Action, the participating laboratories will interact in the frame of 4 partially overlapping working groups (WG) :
WG 1 : "Evolution" - Co-ordinators : A. Huysseune (B) & Y. Sire (F)
WG 2 : "Morphogenesis" - Co-ordinators : P. Sharpe (UK) & I. Thesleff (FIN)
WG 3 : "Cytodifferentiation" - Co-ordinators : D. Tziafas (GR) & B. Thonemann (D)
WG 4 : "Extracellular matrix-mineralisation - Co-ordinators : A. Linde (S) & C. Robinson (UK)
The members of the participating laboratories will join one or several WGs, depending on their interests.
The Action will improve the understanding of inherited and non-inherited abnormalities and dysplasias and will generate progress in the development of adequate therapies in the frame of reparative dentinogenesis and periodontal disease.
During 1996 six Short-Term Scientific Missions were approved.
Work planned
During the first year of Action COST B8 several collaborations were initiated. Outcome will be communicated during the international COST conference "Tooth Morphogenesis and Differentiation" organised in Göteborg (S), 11/15 June 1997. This meeting should also provide opportunities to 1. initiate further collaborations and 2. critically evaluate the European potential in the field, in comparison with USA and Japan.
During 1997 information concerning COST B8 should be available for Internet and E-mail exchanges and discussions should be possible.
During 1998 Action COST B8 should reach the planned level of activity and lead to increased knowledge and new working hypotheses concerning the :
cellular and molecular aspects of species-specific tooth initiation and patterning;
control of tooth-class-specific histo-morphogenesis and dental cytodifferentiation;
molecular mechanisms of normal and abnormal biomineralisations.
Programme(s)
Topic(s)
Call for proposal
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