Mineralized tissues, such as bones or teeth, are essential structures of all vertebrates. They enable rapid movement, protection, and food processing, in addition to providing physiological functions. Although the development, regeneration, and pathogenesis of teeth and bones have been intensely studied, there is currently no tool to accurately follow the dynamics of growth and healing of these vital tissues in space and time. Here, we present the BEE-ST (Bones and tEEth Spatio-Temporal growth monitoring) approach, which allows precise quantification of development, regeneration, remodeling, and healing in any type of calcified tissue across different species. Using mouse teeth as model the turnover rate of continuously growing incisors was quantified, and role of hard/soft diet on molar root growth was shown. Furthermore, the dynamics of bones and teeth growth in lizards, frogs, birds, and zebrafish was uncovered. This approach represents an effective, highly reproducible, and versatile tool that opens up diverse possibilities in developmental biology, bone and tooth healing, tissue engineering, and disease modeling.

• MeSH
• dánio pruhované * MeSH
• kosti a kostní tkáň MeSH
• myši MeSH
• vývoj kostí MeSH
• zubní kořen MeSH
• zuby * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• tisková chyba MeSH

Mechanosensory ion channels are proteins that are sensitive to mechanical forces. They are found in tissues throughout the body and play an important role in bone remodeling by sensing changes in mechanical stress and transmitting signals to bone-forming cells. Orthodontic tooth movement (OTM) is a prime example of mechanically induced bone remodeling. However, the cell-specific role of the ion channels Piezo1 and Piezo2 in OTM has not been investigated yet. Here we first identify the expression of PIEZO1/2 in the dentoalveolar hard tissues. Results showed that PIEZO1 was expressed in odontoblasts, osteoblasts, and osteocytes, while PIEZO2 was localized in odontoblasts and cementoblasts. We therefore used a Piezo1floxed/floxed mouse model in combination with Dmp1cre to inactivate Piezo1 in mature osteoblasts/cementoblasts, osteocytes/cementocytes, and odontoblasts. Inactivation of Piezo1 in these cells did not affect the overall morphology of the skull but caused significant bone loss in the craniofacial skeleton. Histological analysis revealed a significantly increased number of osteoclasts in Piezo1floxed/floxed;Dmp1cre mice, while osteoblasts were not affected. Despite this increased number of osteoclasts, orthodontic tooth movement was not altered in these mice. Our results suggest that despite Piezo1 being crucial for osteoclast function, it may be dispensable for mechanical sensing of bone remodeling.

• MeSH
• buňky pojivové tkáně * MeSH
• iontové kanály MeSH
• myši MeSH
• osteoblasty * MeSH
• osteocyty MeSH
• osteoklasty MeSH
• remodelace kosti MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

• MeSH
• celogenomová asociační studie * MeSH
• energetický metabolismus * genetika   MeSH
• ferritiny genetika   MeSH
• ledviny MeSH
• lidé MeSH
• neandertálci MeSH
• tělesná hmotnost MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Reef-building corals are endangered animals with a complex colonial organization. Physiological mechanisms connecting multiple polyps and integrating them into a coral colony are still enigmatic. Using live imaging, particle tracking, and mathematical modeling, we reveal how corals connect individual polyps and form integrated polyp groups via species-specific, complex, and stable networks of currents at their surface. These currents involve surface mucus of different concentrations, which regulate joint feeding of the colony. Inside the coral, within the gastrovascular system, we expose the complexity of bidirectional branching streams that connect individual polyps. This system of canals extends the surface area by 4-fold and might improve communication, nutrient supply, and symbiont transfer. Thus, individual polyps integrate via complex liquid dynamics on the surface and inside the colony.

• MeSH
• druhová specificita MeSH
• korálnatci * fyziologie   MeSH
• korálové útesy MeSH
• životní prostředí MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.

• MeSH
• buněčná diferenciace * genetika   MeSH
• dospělí MeSH
• epitelové buňky MeSH
• genetická heterogenita MeSH
• kmenové buňky cytologie   MeSH
• lidé MeSH
• mezoderm cytologie   růst a vývoj   metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• modely u zvířat MeSH
• moláry cytologie   růst a vývoj   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• odontoblasty MeSH
• řezáky cytologie   růst a vývoj   MeSH
• vývojová regulace genové exprese MeSH
• zuby cytologie   růst a vývoj   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Facial shape is the basis for facial recognition and categorization. Facial features reflect the underlying geometry of the skeletal structures. Here, we reveal that cartilaginous nasal capsule (corresponding to upper jaw and face) is shaped by signals generated by neural structures: brain and olfactory epithelium. Brain-derived Sonic Hedgehog (SHH) enables the induction of nasal septum and posterior nasal capsule, whereas the formation of a capsule roof is controlled by signals from the olfactory epithelium. Unexpectedly, the cartilage of the nasal capsule turned out to be important for shaping membranous facial bones during development. This suggests that conserved neurosensory structures could benefit from protection and have evolved signals inducing cranial cartilages encasing them. Experiments with mutant mice revealed that the genomic regulatory regions controlling production of SHH in the nervous system contribute to facial cartilage morphogenesis, which might be a mechanism responsible for the adaptive evolution of animal faces and snouts.

• MeSH
• chondrocyty cytologie   účinky léků   metabolismus   MeSH
• čichová sliznice cytologie   účinky léků   růst a vývoj   metabolismus   MeSH
• embryo savčí MeSH
• homeodoménové proteiny genetika   metabolismus   MeSH
• integrasy genetika   metabolismus   MeSH
• kolagen typ II genetika   metabolismus   MeSH
• lidé MeSH
• maxilofaciální vývoj genetika   MeSH
• morfogeneze účinky léků   genetika   MeSH
• mozek účinky léků   růst a vývoj   metabolismus   MeSH
• mutageny aplikace a dávkování   MeSH
• myši transgenní MeSH
• myši MeSH
• nosní chrupavky cytologie   účinky léků   růst a vývoj   metabolismus   MeSH
• obličej anatomie a histologie   embryologie   MeSH
• obličejové kosti cytologie   účinky léků   růst a vývoj   metabolismus   MeSH
• proteiny hedgehog genetika   metabolismus   MeSH
• rekombinantní fúzní proteiny genetika   metabolismus   MeSH
• signální transdukce * MeSH
• tamoxifen aplikace a dávkování   MeSH
• transkripční faktory genetika   metabolismus   MeSH
• vývojová regulace genové exprese MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

G protein-coupled receptors (GPCRs) constitute the largest family of cell surface receptors. They can exist and act as dimers, but the requirement of dimers for agonist-induced signal initiation and structural dynamics remains largely unknown. Frizzled 6 (FZD6) is a member of Class F GPCRs, which bind WNT proteins to initiate signaling. Here, we show that FZD6 dimerizes and that the dimer interface of FZD6 is formed by the transmembrane α-helices four and five. Most importantly, we present the agonist-induced dissociation/re-association of a GPCR dimer through the use of live cell imaging techniques. Further analysis of a dimerization-impaired FZD6 mutant indicates that dimer dissociation is an integral part of FZD6 signaling to extracellular signal-regulated kinases1/2. The discovery of agonist-dependent dynamics of dimers as an intrinsic process of receptor activation extends our understanding of Class F and other dimerizing GPCRs, offering novel targets for dimer-interfering small molecules.Frizzled 6 (FZD6) is a G protein-coupled receptor (GPCR) involved in several cellular processes. Here, the authors use live cell imaging and spectroscopy to show that FZD6 forms dimers, whose association is regulated by WNT proteins and that dimer dissociation is crucial for FZD6 signaling.

• MeSH
• dimerizace MeSH
• frizzled receptory metabolismus   MeSH
• HEK293 buňky MeSH
• lidé MeSH
• protein Wnt 5a metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cartilaginous structures are at the core of embryo growth and shaping before the bone forms. Here we report a novel principle of vertebrate cartilage growth that is based on introducing transversally-oriented clones into pre-existing cartilage. This mechanism of growth uncouples the lateral expansion of curved cartilaginous sheets from the control of cartilage thickness, a process which might be the evolutionary mechanism underlying adaptations of facial shape. In rod-shaped cartilage structures (Meckel, ribs and skeletal elements in developing limbs), the transverse integration of clonal columns determines the well-defined diameter and resulting rod-like morphology. We were able to alter cartilage shape by experimentally manipulating clonal geometries. Using in silico modeling, we discovered that anisotropic proliferation might explain cartilage bending and groove formation at the macro-scale.

• MeSH
• biologické modely MeSH
• chrupavka embryologie   MeSH
• myši MeSH
• obratlovci embryologie   MeSH
• počítačová simulace MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cranial neural crest cells populate the future facial region and produce ectomesenchyme-derived tissues, such as cartilage, bone, dermis, smooth muscle, adipocytes, and many others. However, the contribution of individual neural crest cells to certain facial locations and the general spatial clonal organization of the ectomesenchyme have not been determined. We investigated how neural crest cells give rise to clonally organized ectomesenchyme and how this early ectomesenchyme behaves during the developmental processes that shape the face. Using a combination of mouse and zebrafish models, we analyzed individual migration, cell crowd movement, oriented cell division, clonal spatial overlapping, and multilineage differentiation. The early face appears to be built from multiple spatially defined overlapping ectomesenchymal clones. During early face development, these clones remain oligopotent and generate various tissues in a given location. By combining clonal analysis, computer simulations, mouse mutants, and live imaging, we show that facial shaping results from an array of local cellular activities in the ectomesenchyme. These activities mostly involve oriented divisions and crowd movements of cells during morphogenetic events. Cellular behavior that can be recognized as individual cell migration is very limited and short-ranged and likely results from cellular mixing due to the proliferation activity of the tissue. These cellular mechanisms resemble the strategy behind limb bud morphogenesis, suggesting the possibility of common principles and deep homology between facial and limb outgrowth.

• MeSH
• anatomické modely MeSH
• buněčná diferenciace * MeSH
• buněčné klony cytologie   MeSH
• crista neuralis cytologie   MeSH
• dánio pruhované MeSH
• ektoderm cytologie   embryologie   MeSH
• exprese genu MeSH
• fenotyp MeSH
• mezoderm cytologie   embryologie   MeSH
• morfogeneze * MeSH
• myši MeSH
• obličej embryologie   MeSH
• organogeneze * MeSH
• pohyb buněk MeSH
• reportérové geny MeSH
• zobrazování trojrozměrné MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH