Ectodysplasin (Eda) plays important roles in both shaping the developing tooth and establishing the number of teeth within the tooth row. Sonic hedgehog (Shh) has been shown to act downstream of Eda and is involved in the initiation of tooth development. Eda-/- mice possess hypoplastic and hypomineralized incisors and show changes in tooth number in the molar region. In the present study we used 3D reconstruction combined with expression analysis, cell lineage tracing experiments, and western blot analysis in order to investigate the formation of the incisor germs in Eda-/- mice. We show that a lack of functional Eda protein during early stages of incisor tooth germ development had minimal impact on development of the early expression of Shh in the incisor, a region proposed to mark formation of a rudimental incisor placode and act as an initiating signalling centre. In contrast, deficiency of Eda protein had a later impact on expression of Shh in the primary enamel knot of the functional tooth. Eda-/- mice had a smaller region where Shh was expressed, and a reduced contribution from Shh descendant cells. The reduction in the enamel knot led to the formation of an abnormal enamel organ creating a hypoplastic functional incisor. Eda therefore appears to influence the spatial formation of the successional signalling centres during odontogenesis.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: We had a case in which three consecutive pregnancies resulted in birth of three children with an orofacial cleft. Their mother suffered from bronchial asthma and was treated using symbicort (corticosteroid budesonide plus bronchodilator formoterol) during her pregnancies. A hypothesis was assessed: these anti-asthmatics can induce an orofacial cleft in experimental model. MATERIALS AND METHODS: A single administration of one of five increasing doses (including therapeutically used ones) of Symbicort, budesonide or formoterol was injected into the amnion of a chick embryo on day 4 or 5 of incubation. The teratogenic/lethal effects of the anti-asthmatics were assessed on a total of 600 embryos. RESULTS: For budesonide, the teratogenic/lethal effect started at a dose 0.003 μg per embryo, for formoterol at 0.3 μg and for Symbicort 0.03 μg. Orofacial clefts and gastroschisis after exposure were found for all three anti-asthmatics. Heart septum defects occurred after exposure to formoterol. CONCLUSION: The present results support those clinical/epidemiological studies pointing out that anti-asthmatics have the potential to induce orofacial clefts, gastroschisis and heart malformations during prenatal development in human.

• MeSH
• antiastmatika * MeSH
• aplikace inhalační MeSH
• budesonid škodlivé účinky   MeSH
• dítě MeSH
• dvojitá slepá metoda MeSH
• ethanolaminy škodlivé účinky   MeSH
• formoterol fumarát škodlivé účinky   MeSH
• gastroschiza * chemicky indukované   MeSH
• kombinace léků budesonid a formoterol MeSH
• kuřecí embryo MeSH
• lidé MeSH
• rozštěp patra * chemicky indukované   MeSH
• rozštěp rtu * chemicky indukované   MeSH
• srdeční septum MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kuřecí embryo MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Within the mandible, the odontogenic and osteogenic mesenchymes develop in a close proximity and form at about the same time. They both originate from the cranial neural crest. These two condensing ecto-mesenchymes are soon separated from each other by a very loose interstitial mesenchyme, whose cells do not express markers suggesting a neural crest origin. The two condensations give rise to mineralized tissues while the loose interstitial mesenchyme, remains as a soft tissue. This is crucial for proper anchorage of mammalian teeth. The situation in all three regions of the mesenchyme was compared with regard to cell heterogeneity. As the development progresses, the early phenotypic differences and the complexity in cell heterogeneity increases. The differences reported here and their evolution during development progressively specifies each of the three compartments. The aim of this review was to discuss the mechanisms underlying condensation in both the odontogenic and osteogenic compartments as well as the progressive differentiation of all three mesenchymes during development. Very early, they show physical and structural differences including cell density, shape and organization as well as the secretion of three distinct matrices, two of which will mineralize. Based on these data, this review highlights the consecutive differences in cell-cell and cell-matrix interactions, which support the cohesion as well as mechanosensing and mechanotransduction. These are involved in the conversion of mechanical energy into biochemical signals, cytoskeletal rearrangements cell differentiation, or collective cell behavior.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Sprouty proteins are modulators of the MAPK/ERK pathway. Amongst these, Sprouty2 (SPRY2) has been investigated as a possible factor that takes part in the initial phases of osteogenesis. However, the in vivo context has not yet been investigated and the underlying mechanisms taking place in vitro remain unknown. Therefore, in this study, the impact of Spry2 deficiency was examined in the developing tibias of Spry2 deficient (-/-) mouse. The investigation was performed when the osteogenic zone became clearly visible and when all three basic bone cells types were present. The main markers of osteoblasts, osteocytes and osteoclasts were evaluated by immunohistochemistry and RT-PCR. RT-PCR showed that the expression of Sost was 3.5 times higher in Spry2-/- than in the wild-type bone, which pointed to a still unknown mechanism of action of SPRY2 on the differentiation of osteocytes. The up-regulation of Sost was independent of Hif-1α expression and could not be related to its positive regulator, Runx2, since none of these factors showed an increased expression in the bone of Spry2-/- mice. Regarding the RANK/RANKL/OPG pathway, the Spry2-/- showed an increased expression of Rank, but no significant change in the expression of Rankl and Opg. Thanks to these results, the impact of Spry2 deletion is shown for the first time in the developing bone as a complex organ including, particularly, an effect on osteoblasts (Runx2) and osteocytes (Sost). This might explain the previously reported decrease in bone formation in postnatal Spry2-/- mice.

• MeSH
• buněčná diferenciace MeSH
• cytoplazma metabolismus   MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• ligand RANK metabolismus   MeSH
• membránové proteiny genetika   fyziologie   MeSH
• myši inbrední ICR MeSH
• myši knockoutované MeSH
• myši MeSH
• osteoblasty cytologie   metabolismus   MeSH
• osteocyty cytologie   metabolismus   MeSH
• osteogeneze * MeSH
• osteoklasty cytologie   metabolismus   MeSH
• osteoprotegerin metabolismus   MeSH
• proliferace buněk MeSH
• protein-serin-threoninkinasy genetika   fyziologie   MeSH
• vývoj kostí MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To compare the influence of 3 different time protocols of cleft lip and palate operations on the growth of the dentoalveolar arch in patients with unilateral cleft lip and palate (UCLP). MATERIALS AND METHODS: We evaluated 64 plaster casts of 8-year-old boys with UCLP operated on according to 3 different time protocols: lip repair at the age of 6 months and palate repair at 4 years, lip repair at 3 months and palate repair at 9 months, and neonatal lip repair and palate repair at 9 months. The control group contained 13 plaster casts of 8-year-old boys. The dentoalveolar arch width was measured between deciduous canines and between the second deciduous molars; the length was measured between incisive papilla and the line connecting both tuber maxillae. RESULTS: All measured distances were statistically significantly smaller in boys with UCLP than in the control group. Intercanine width was not statistically significantly different between the patients operated on according to the different time protocols. In comparison to the lip repair at 6 months and palate repair at 4 years, the intermolar width was statistically significantly smaller in the group with neonatal lip repair; the alveolar arch length was statistically significantly shorter in both groups with lip repair performed neonatally or at 3 months. CONCLUSIONS: The length of the dentoalveolar arch is shorter after surgical repair of cleft lip neonatally or at the age of 3 months. Cleft palate repair at 9 months can contribute to a reduction in the width of the dentoalveolar arch.

• MeSH
• dítě MeSH
• lidé MeSH
• maxila MeSH
• novorozenec MeSH
• ret * chirurgie   MeSH
• rozštěp patra * chirurgie   MeSH
• rozštěp rtu * chirurgie   MeSH
• zubní oblouk anatomie a histologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Choosing the optimal season for conception is a part of family planning since it can positively influence the pregnancy outcome. Changes in the monthly number of infants born with a birth defect can signal prenatal damage - death or malformation - related to a harmful seasonal factor. The aim of our paper was to search for possible seasonal differences in the numbers of new-borns with an orofacial cleft and thus for a period of conception that can increase the risk of orofacial cleft development. METHODS: Mean monthly numbers of live births in the Bohemia region of the Czech Republic during the years 1964-2000 were compared within a group of 5619 new-borns with various types of orofacial clefts and the control group derived from natality data on 3,080,891 new-borns. RESULTS: The control group exhibited regular seasonal variation in the monthly numbers of new-borns: significantly more babies born during March-May and fewer babies born during October-December. Similar natural seasonal variation was also found in the group of babies with an orofacial cleft. However, after subdividing the cleft group according to gender and cleft type, in comparison to controls, significant differences appeared in the number of new-born girls with cleft lip during January-March and in the number of boys born with cleft palate in April - May. CONCLUSIONS: We found significant differences from controls in the number of new-born girls with CL and boys with CP, whose dates of birth correspond to conception from April to August and to the estimated prenatal critical period for cleft formation from May to October. The latter period includes the warm season, when various injurious physical, chemical and biological factors may act on a pregnant woman. This finding should be considered in pregnancy planning. Future studies are necessary to investigate the putative injurious factors during the warm season that can influence pregnancy outcome.

• MeSH
• charakteristiky bydlení MeSH
• incidence MeSH
• lidé MeSH
• novorozenec MeSH
• retrospektivní studie MeSH
• roční období * MeSH
• rozštěp patra epidemiologie   MeSH
• rozštěp rtu epidemiologie   MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

In this review, classical data on the early steps in human odontogenesis are summarized and updated with specific insights into the development of the upper and lower embryonic jaws to help in understanding some oral pathologies. The initial step of human odontogenesis is classically characterized by two parallel horseshoe-shaped epithelial laminae. These originate from the oral epithelium and an ingrowth into the jaw mesenchyme: the internal dental lamina gives rise to deciduous tooth primordia, while the external vestibular lamina represents the developmental base of the oral vestibule. However, a more complex situation was revealed by recent studies combining analyses of the dental and adjacent oral epithelia on histological sections and computer-aided three-dimensional (3D) reconstructions during the 2nd month of human embryonic development. The dental epithelium forms a mound, where swellings appear later, corresponding to the individual primordia of deciduous teeth. External to the developing deciduous dentition, the 3D reconstructions do not show any continuous vestibular lamina but instead a complex of discontinuous epithelial bulges and ridges. The patterns of these epithelial structures and their relationship to the dental epithelium differ not only between the upper and lower jaws but also between the lip and cheek segments in each jaw. Knowledge of early odontogenesis may help in understanding some oral pathologies. For example, the human lateral incisor has a dual origin: it arises in the area of fusion between the medial nasal and maxillary facial processes and involves material from these two regions. Such a dual origin at the site of fusion of facial processes represents a predisposition to developmental vulnerability for the upper lateral incisor, resulting in its frequent anomalies (absence, hypoplasia, duplication), especially in patients with a cleft lip and/or jaw. Other pathologies, such as a minute supernumerary tooth, desmoplastic ameloblastoma or extraosseous odontogenic cysts are located external to the upper or lower dentition, and might be derived from structures that transiently appear during early development of the oral vestibule in humans.

• MeSH
• čelisti embryologie   MeSH
• dentice MeSH
• lidé MeSH
• zuby embryologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Comparative transcriptomics can answer many questions in developmental and evolutionary developmental biology. Most transcriptomic studies start by showing global patterns of variation in transcriptomes that differ between species or organs through developmental time. However, little is known about the kinds of expression differences that shape these patterns. RESULTS: We compared transcriptomes during the development of two morphologically distinct serial organs, the upper and lower first molars of the mouse. We found that these two types of teeth largely share the same gene expression dynamics but that three major transcriptomic signatures distinguish them, all of which are shaped by differences in the relative abundance of different cell types. First, lower/upper molar differences are maintained throughout morphogenesis and stem from differences in the relative abundance of mesenchyme and from constant differences in gene expression within tissues. Second, there are clear time-shift differences in the transcriptomes of the two molars related to cusp tissue abundance. Third, the transcriptomes differ most during early-mid crown morphogenesis, corresponding to exaggerated morphogenetic processes in the upper molar involving fewer mitotic cells but more migrating cells. From these findings, we formulate hypotheses about the mechanisms enabling the two molars to reach different phenotypes. We also successfully applied our approach to forelimb and hindlimb development. CONCLUSIONS: Gene expression in a complex tissue reflects not only transcriptional regulation but also abundance of different cell types. This knowledge provides valuable insights into the cellular processes underpinning differences in organ development. Our approach should be applicable to most comparative developmental contexts.

• MeSH
• epitel embryologie   metabolismus   MeSH
• mezoderm embryologie   metabolismus   MeSH
• moláry embryologie   metabolismus   MeSH
• morfogeneze genetika   MeSH
• mozaicismus MeSH
• myši MeSH
• organogeneze genetika   MeSH
• signální transdukce MeSH
• transkriptom * MeSH
• vývojová biologie * metody   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Recently, it has been found that spontaneous mutation Lx (polydactyly-luxate syndrome) in the rat is determined by deletion of a conserved intronic sequence of the Plzf (Promyelocytic leukemia zinc finger protein) gene. In addition, Plzf is a prominent candidate gene for quantitative trait loci (QTLs) associated with cardiac hypertrophy and fibrosis in the spontaneously hypertensive rat (SHR). In the current study, we tested the effects of Plzf gene targeting in the SHR using TALENs (transcription activator-like effector nucleases). SHR ova were microinjected with constructs pTAL438/439 coding for a sequence-specific endonuclease that binds to target sequence in the first coding exon of the Plzf gene. Out of 43 animals born after microinjection, we detected a single male founder. Sequence analysis revealed a deletion of G that resulted in frame shift mutation starting in codon 31 and causing a premature stop codon at position of amino acid 58. The Plzftm1Ipcv allele is semi-lethal since approximately 95% of newborn homozygous animals died perinatally. All homozygous animals exhibited manifestations of a caudal regression syndrome including tail anomalies and serious size reduction and deformities of long bones, and oligo- or polydactyly on the hindlimbs. The heterozygous animals only exhibited the tail anomalies. Impaired development of the urinary tract was also revealed: one homozygous and one heterozygous rat exhibited a vesico-ureteric reflux with enormous dilatation of ureters and renal pelvis. In the homozygote, this was combined with a hypoplastic kidney. These results provide evidence for the important role of Plzf gene during development of the caudal part of a body-column vertebrae, hindlimbs and urinary system in the rat.

• MeSH
• alely MeSH
• DNA vazebné proteiny nedostatek   genetika   metabolismus   MeSH
• exony MeSH
• genotyp MeSH
• genový targeting MeSH
• heterozygot MeSH
• homozygot MeSH
• krysa rodu rattus MeSH
• lokus kvantitativního znaku MeSH
• mnohočetné abnormality genetika   patologie   veterinární   MeSH
• ocas abnormality   MeSH
• polydaktylie genetika   patologie   veterinární   MeSH
• posunová mutace MeSH
• potkani inbrední SHR MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• TALENs genetika   metabolismus   MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• abnormality zubů genetika   MeSH
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• prenatální diagnóza MeSH
• primární prevence metody   MeSH
• řezáky patologie   MeSH
• rozštěp patra * epidemiologie   genetika   prevence a kontrola   MeSH
• rozštěp rtu * epidemiologie   genetika   prevence a kontrola   MeSH
• ultrasonografie prenatální MeSH
• vrozené vady epidemiologie   etiologie   prevence a kontrola   MeSH
• vývoj plodu genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• práce podpořená grantem MeSH