Wnt signaling during tooth replacement in zebrafish (Danio rerio) : pitfalls and perspectives

The canonical (13-catenin dependent) Wnt signaling pathway has emerged as a likely candidate for regulating tooth replacement in continuously renewing dentitions. So far, the involvement of canonical Wnt signaling has been experimentally demonstrated predominantly in amniotes. These studies tend to show stimulation of tooth formation by activation of the Wnt pathway, and inhibition of tooth formation when blocking the pathway. Here, we report a strong and dynamic expression of the soluble V\int inhibitor dickkopfl (dkkl) in developing zebrafish (Danio rerio) tooth germs, suggesting an active repression of V\int signaling during morphogenesis and cytodifferentiation of a tooth, and derepression of Wnt signaling during start of replacement tooth formation. To further analyse the role of Wnt signaling, we used different gain-of-function approaches. These yielded disjunct results, yet none of them indicating enhanced tooth replacement. Thus, masterblind (mbl) mutants, defective in axinl, mimic overexpression of Mt, but display a normally patterned dentition in which teeth are replaced at the appropriate times and positions. Activating the pathway with LICI had variable outcomes, either resulting in the absence, or the delayed formation, of first-generation teeth, or yielding a regular dentition with normal replacement, but no supernumerary teeth or accelerated tooth replacement. The failure so far to influence tooth replacement in the zebrafish by perturbing Wnt signaling is discussed in the light of (i) potential technical pitfalls related to dose- or time-dependency, (ii) the complexity of the canonical V\int pathway, and (iii) species-specific differences in the nature and activity of pathway components. Finally, we emphasize the importance of in-depth knowledge of the wild-type pattern for reliable interpretations. It is hoped that our analysis can be inspiring to critically assess and elucidate the role of V\int signaling in tooth development in polyphyodonts

Zebrafish teeth as a model for repetitive epithelial morphogenesis: dynamics of E-cadherin expression

Background: The development of teeth is the result of interactions between competent mesenchyme and epithelium, both of which undergo extensive morphogenesis. The importance of cell adhesion molecules in morphogenesis has long been acknowledged but remarkably few studies have focused on the distribution and function of these molecules in tooth development. Results: We analyzed the expression pattern of an important epithelial cadherin, E-cadherin, during the formation of first-generation teeth as well as replacement teeth in the zebrafish, using in situ hybridization and whole mount immunostaining to reveal mRNA expression and protein distribution. E-cadherin was detected in every layer of the enamel organ during the different stages of tooth development, but there were slight differences between first-generation and replacement teeth in the strength and distribution of the signal. The dental papilla, which is derived from the mesenchyme, did not show any expression. Remarkably, the crypts surrounding the functional teeth showed an uneven distribution of E-cadherin throughout the pharyngeal region. Conclusions: The slight differences between E-cadherin expression in zebrafish teeth and developing mouse and human teeth are discussed in the light of fundamental differences in structural and developmental features of the dentition between zebrafish and mammals. Importantly, the uninterrupted expression of E-cadherin indicates that down-regulation of E-cadherin is not required for formation of an epithelial tooth bud. Further research is needed to understand the role of other cell adhesion systems during the development of teeth and the formation of replacement teeth

Serbia and Montenegro

Die Verfasser untersuchen die Auswirkungen der Europäisierung auf das Verhältnis zwischen Serbien und Montenegro. Die Aussicht auf eine zukünftige EU-Mitgliedschaft und die aktive Vermittlungstätigkeit der EU führten mit der Unterzeichnung des Belgrader Abkommens im März 2002 zur Schaffung einer prekären gemeinsamen Staatsformation. Die 'Staatenunion Serbien und Montenegro' ist ein hybrides Modell mit föderalen wie konföderalen Elementen und hat bisher in keiner der beiden Teilrepubliken politische Begeisterung wecken können. Politische Gruppen in Serbien wie in Montenegro bezweifeln ihre Überlebensfähigkeit, Befürworter nationaler Unabhängigkeit haben nach der Schaffung des gemeinsamen Staates Zulauf erfahren. Die Zukunft der 'Staatenunion' hängt entscheidend davon ab, in wie weit die EU fähig und willens ist, die Umsetzung des Belgrader Abkommens zu überwachen und Zwistigkeiten zwischen den beiden Republiken über Fragen im Zusammenhang mit deren gemeinsamem Antrag auf Aufnahme in die EU zu schlichten. (ICEÜbers)'This chapter analyzes the impact of Europeanization on the Serbia - Montenegro relationship. The EU framework through the prospect of future membership and the EU active mediation through conditionality and socialization converged to put in place a precarious common state structure with the signing of the Belgrade Agreement in March 2002. The State Union of Serbia and Montenegro is a hybrid institutional model combining federal features and confederal elements. It has failed to generate consensual political support in either of the republics. Its viability has been questioned by political formations in both Serbia and Montenegro while pro independence forces have been strengthened after the creation of the common state. The future of the State Union depends critically on the capacity and willingness of the EU to supervise the implementation of the Belgrade Agreement and arbitrate the disagreements between the two republics on issues related to their joint EU membership bid.' (author's abstract

Periderm invasion contributes to epithelial formation in the teleost pharynx

The gnathostome pharyngeal cavity functions in food transport and respiration. In amniotes the mouth and nares are the only channels allowing direct contact between internal and external epithelia. In teleost fish, gill slits arise through opening of endodermal pouches and connect the pharynx to the exterior. Using transgenic zebrafish lines, cell tracing, live imaging and different markers, we investigated if pharyngeal openings enable epithelial invasion and how this modifies the pharyngeal epithelium. We conclude that in zebrafish the pharyngeal endoderm becomes overlain by cells with a peridermal phenotype. In a wave starting from pouch 2, peridermal cells from the outer skin layer invade the successive pouches until halfway their depth. Here the peridermal cells connect to a population of cells inside the pharyngeal cavity that express periderm markers, yet do not invade from outside. The latter population expands along the midline from anterior to posterior until the esophagus-gut boundary. Together, our results show a novel role for the periderm as an internal epithelium becomes adapted to function as an external surface.Agência financiadora Ghent University Research Fund - BOF24J2015001401 Cancer Prevention Research Institute of Texas - RR140077info:eu-repo/semantics/publishedVersio