Tooth formation requires complex signaling interactions both within the oral epithelium and between the epithelium and the underlying mesenchyme. Previous studies of the Wnt/β-catenin pathway have shown that tooth formation is partly inhibited in loss-of-function mutants, and gain-of-function mutants have perturbed tooth morphology. However, the stage at which Wnt signaling is first important in tooth formation remains unclear. Here, using an Fgf8-promoter-driven, and therefore early, deletion of β-catenin in mouse molar epithelium, we found that loss of Wnt/β-catenin signaling completely deletes the molar tooth, demonstrating that this pathway is central to the earliest stages of tooth formation. Early expression of a dominant-active β-catenin protein also perturbs tooth formation, producing a large domed evagination at early stages and supernumerary teeth later on. The early evaginations are associated with premature mesenchymal condensation marker, and are reduced by inhibition of condensation-associated collagen synthesis. We propose that invagination versus evagination morphogenesis is regulated by the relative timing of epithelial versus mesenchymal cell convergence regulated by canonical Wnt signaling. Together, these studies reveal new aspects of Wnt/β-catenin signaling in tooth formation and in epithelial morphogenesis more broadly.

• Klíčová slova
• Epithelial invagination, Morphogenesis, Mouse, Tooth development, Wnt signaling,
• MeSH
• beta-katenin metabolismus   MeSH
• epitel metabolismus   MeSH
• epitelové buňky cytologie   metabolismus   MeSH
• mezoderm metabolismus   MeSH
• moláry cytologie   růst a vývoj   metabolismus   MeSH
• morfogeneze fyziologie   MeSH
• myši MeSH
• odontogeneze genetika   fyziologie   MeSH
• proliferace buněk MeSH
• signální dráha Wnt fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• beta-katenin MeSH
• CTNNB1 protein, mouse MeSH Prohlížeč

Do developmental systems preferentially produce certain types of variation that orient phenotypic evolution along preferred directions? At different scales, from the intra-population to the interspecific, the murine first upper molar shows repeated anterior elongation. Using a novel quantitative approach to compare the development of two mouse strains with short or long molars, we identified temporal, spatial and functional differences in tooth signaling center activity, that arise from differential tuning of the activation-inhibition mechanisms underlying tooth patterning. By tracing their fate, we could explain why only the upper first molar reacts via elongation of its anterior part. Despite a lack of genetic variation, individuals of the elongated strain varied in tooth length and the temporal dynamics of their signaling centers, highlighting the intrinsic instability of the upper molar developmental system. Collectively, these results reveal the variational properties of murine molar development that drive morphological evolution along a line of least resistance.

Over time species develop random mutations in their genetic sequence that causes their form to change. If this new form increases the survival of a species it will become favored through natural selection and is more likely to get passed on to future generations. But, the evolution of these new traits also depends on what happens during development. Developmental mechanisms control how an embryo progresses from a single cell to an adult organism made of many cells. Mutations that alter these processes can influence the physical outcome of development, and cause a new trait to form. This means that if many different mutations alter development in a similar way, this can lead to the same physical change, making it ‘easy’ for a new trait to repeatedly occur. Most of the research has focused on finding the mutations that underlie repeated evolution, but rarely on identifying the role of the underlying developmental mechanisms. To bridge this gap, Hayden et al. investigated how changes during development influence the shape and size of molar teeth in mice. In some wild species of mice, the front part of the first upper molar is longer than in other species. This elongation, which is repeatedly found in mice from different islands, likely came from developmental mechanisms. Tooth development in mice has been well-studied in the laboratory, and Hayden et al. started by identifying two strains of laboratory mice that mimic the teeth seen in their wild cousins, one with elongated upper first molars and another with short ones. Comparing how these two strains of mice developed their elongated or short teeth revealed key differences in the embryonic structures that form the upper molar and cause it to elongate. Further work showed that variations in these embryonic structures can even cause mice that are genetically identical to have longer or shorter upper first molars. These findings show how early differences during development can lead to small variations in form between adult species of mice. This study highlights how studying developmental differences as well as genetic sequences can further our understanding of how different species evolved.

• Klíčová slova
• developmental biology, developmental constraint, evo-devo, evolutionary biology, line of least resistance, molar, mouse, rodent,
• MeSH
• biologická evoluce MeSH
• biologická variabilita populace fyziologie   MeSH
• embryo savčí MeSH
• fenotyp MeSH
• moláry anatomie a histologie   růst a vývoj   MeSH
• myši MeSH
• prořezávání zubů fyziologie   MeSH
• signální transdukce MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Vertebrate dentitions arise at various places within the oropharyngeal cavity including the jaws, the palate, or the pharynx. These dentitions develop in a highly organized way, where new tooth germs are progressively added adjacent to the initiator center, the first tooth. At the same time, the places where dentitions develop house the contact zones between the outer ectoderm and the inner endoderm, and this colocalization has instigated various suggestions on the roles of germ layers for tooth initiation and development. Here, we study development of the axolotl dentition, which is a complex of five pairs of tooth fields arranged into the typically tetrapod outer and inner dental arcades. By tracking the expression patterns of odontogenic genes, we reason that teeth of both dental arcades originate from common tooth-competent zones, one present on the mouth roof and one on the mouth floor. Progressive compartmentalization of these zones and a simultaneous addition of new tooth germs distinct for each prospective tooth field subsequently control the final shape and composition of the axolotl dentition. Interestingly, by following the fate of the GFP-labeled oral ectoderm, we further show that, in three out of five tooth field pairs, the first tooth develops right at the ecto-endodermal boundary. Our results thus indicate that a single tooth-competent zone gives rise to both dental arcades of a complex tetrapod dentition. Further, we propose that the ecto-endodermal boundary running through this zone should be accounted for as a potential source of instruction factors instigating the onset of the odontogenic program.

• Klíčová slova
• axolotl, dental arcades, ectoderm, endoderm, initiation, patterning, tooth development,
• Publikační typ
• časopisecké články MeSH