Cyril Charles

Background Unlike many vertebrates with continuous dental replacement, mammals have a maximum of two dental generations. Due to the absence of dental replacement in the laboratory mouse, the mechanisms of the mammalian tooth replacement system are poorly known. In this study, we use the European rabbit as a model for mammalian tooth development and replacement. Results We provide data on some key regulators of tooth development. We detected the presence of SOX2 in both the replacement dental lamina and the rudimentary successional dental lamina of unreplaced molars, indicating that SOX2 may not be sufficient to initiate and maintain tooth replacement. We showed that Shh does not seem to be directly involved in tooth replacement. The transient presence of the rudimentary successional dental lamina in the molar allowed us to identify genes that could be essential for the initiation or the maintenance of tooth replacement. Hence, the locations of Sostdc1, RUNX2 and LEF1 varie between the deciduous premolar, the replacement premolar and the molar, indicating possible roles in tooth replacement. Conclusion According to our observations, initiation and the maintenance of tooth replacement correlate with the presence of LEF1⁺ cells and the absence of both mesenchymal RUNX2 and epithelial Sostdc1⁺ cells.

Weaning practices differ among great apes and likely diverged during the course of human evolution, but behavioral inference from the fossil record is hampered by a lack of unambiguous biomarkers. Here, we show that early-life dietary transitions are recorded in human deciduous tooth enamel as marked variations in Ca isotope ratios (δ^44/42Ca). Using a sequential microsampling method along the enamel growth axis, we collected more than 150 enamel microsamples from 51 deciduous teeth of 12 different modern human individuals of known dietary histories, as well as nine enamel samples from permanent third molars. We measured and reconstructed the evolution of ⁴⁴Ca/⁴²Ca ratios in enamel from in utero development to first months of postnatal development. We show that the observed variations of δ^44/42Ca record a transition from placental nutrition to an adult-like diet and that Ca isotopes reflect the duration of the breastfeeding period experienced by each infant. Typically, the δ^44/42Ca values of individuals briefly or not breastfed show a systematic increase during the first 5–10 mo, whereas individuals with long breastfeeding histories display no measurable variation in δ^44/42Ca of enamel formed during this time. The use of Ca isotope analysis in tooth enamel allows microsampling and offers an independent approach to tackle challenging questions related to past population dynamics and evolution of weaning practices in hominins.

Luminescent core–shell crystals based on lanthanide tris‐dipicolinate complexes were obtained from the successive growing of two different lanthanide complex layers. Selective or simultaneous emission of each part of the crystal can be achieved by a careful choice of the excitation wavelength.

The question of phenotypic convergence across a signalling pathway has important implications for both developmental and evolutionary biology. The ERK-MAPK cascade is known to play a central role in dental development, but the relative roles of its components remain unknown. Here we investigate the diversity of dental phenotypes in Spry2^−/−, Spry4^−/− and Rsk2^−/Y mice, including the incidence of extra teeth, which were lost in the mouse lineage 45 million years ago (Ma). In addition, Sprouty-specific anomalies mimic a phenotype that is absent in extant mice but present in mouse ancestors prior to 9 Ma. Although the mutant lines studied display convergent phenotypes, each gene has a specific role in tooth number determination and crown patterning. The similarities found between teeth in fossils and mutants highlight the pivotal role of the ERK-MAPK cascade during the evolution of the dentition in rodents.

Mammalian dental morphology is under strong evolutionary pressure because of its importance for mastication and diet. While the mechanisms underlying tooth development have been widely studied in model organisms, the role of genetic regulatory elements in patterning the different elements of the occlusal surface and crown height across species is not well understood. Previous studies showed that Fibroblast Growth Factor (FGF) genes are important regulators of tooth development that influence morphological variation. We hypothesized that inter-specific variation in rodent dental morphology could be governed by nucleotide variation in genetic regulatory elements that modulate the spatial and temporal expression of the genes encoding FGF signaling molecules. In this study, we compared the variation in dental morphology across nine taxa of rodents to the variation in sequences of non-coding evolutionary conserved regions (ECRs) of Fgf3, 4, 8, 9, and 10. We correlated the variation in molar tooth cusp shape and the evolution of high molar crowns (hypsodonty) to the patterns of sequence variation in two ECRs, Fgf10ECR3, and Fgf9ECR1, respectively. By conducting luciferase and electrophoretic mobility shift assays, we determined that these ECRs could function as enhancers. These data suggest that emergence of hypsodonty and occlusal cusp patterning may have happened through the evolutionary changes in enhancers, such as Fgf9ECR1 and Fgf10ECR3, which affected the expression of major signaling molecules involved in tooth development.

We provide novel data on vertebral ontogeny in the mouse, the mammalian model-of-choice for developmental studies. Most previous studies on ossification sequences in mice have focused on pooled elements of the spine (cervicals, thoracics, lumbars, sacrals, and caudals). Here, we contribute data on ossification sequences in the neural arches and centra to provide a comparative basis upon which to evaluate mammalian diversity of the axial skeleton. In attempt to explain the ossification pattern observed, we compared our observations with the phenotype of Cdx over-expresser mice. We use high-resolution X-ray microtomography and clearing and staining techniques to quantify the precise sequential ossification pattern of the mouse spine. We show that micro-CT scans perform better in all cases whereas clearing and staining exhibit sensitivity to the presence of semi-opaque tissue. We observe that the centra of wild-type mice always ossify after neural arches and that the ossification of the neural arches proceeds from two loci. The ossification of the centra appears more complex, especially in the neck where ossification is delayed and does not just follow the order of the vertebrae along the anterior–posterior axis. Our findings also suggest that Cdx genes' expression levels may be involved in the delayed ossification in the neck centra. J. Exp. Zool. (Mol. Dev. Evol.) 322B: 631–642, 2014.

Thyroid hormone (T3) is required for postnatal skeletal growth. It exerts its effect by binding to nuclear receptors, TRs including TRα1 and TRβ1, which are present in most cell types. These cell types include chondrocytes and osteoblasts, the interactions of which are known to regulate endochondral bone formation. In order to analyze the respective functions of T3 stimulation in chondrocytes and osteoblasts during postnatal growth, we use Cre/loxP recombination to express a dominant-negative TRα1L400R mutant receptor in a cell-specific manner. Phenotype analysis revealed that inhibiting T3 response in chondrocytes is sufficient to reproduce the defects observed in hypothyroid mice, not only for cartilage maturation, but also for ossification and mineralization. TRα1L400R in chondrocytes also results in skull deformation. In the meantime, TRα1L400R expression in mature osteoblasts has no visible effect. Transcriptome analysis identifies a number of changes in gene expression induced by TRα1L400R in cartilage. These changes suggest that T3 normally cross talks with several other signaling pathways to promote chondrocytes proliferation, differentiation, and skeletal growth.