Anti-asthma Drugs Formoterol and Budesonide (Symbicort) Induce Orofacial Clefts, Gastroschisis and Heart Septum Defects in an Model.

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.

Correction: Targeting of the Plzf Gene in the Rat by Transcription Activator-Like Effector Nuclease Results in Caudal Regression Syndrome in Spontaneously Hypertensive Rats.

[This corrects the article DOI: 10.1371/journal.pone.

Dentoalveolar Arch Dimensions in UCLP Boys After Neonatal Cheiloplasty or After Lip Surgery at the Age of 3 or 6 Months.

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.

Long-term significant seasonal differences in the numbers of new-borns with an orofacial cleft in the Czech Republic - a retrospective study.

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.

Targeting of the Plzf Gene in the Rat by Transcription Activator-Like Effector Nuclease Results in Caudal Regression Syndrome in Spontaneously Hypertensive Rats.

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).

3-D shape analysis of palatal surface in patients with unilateral complete cleft lip and palate.

Facial development of patients with unilateral complete cleft lip and palate (UCLP) is associated with many problems including deformity of the palate. The aim of this study was to evaluate palatal morphology and variability in patients with UCLP compared with Czech norms using methods of geometric morphometrics. The study was based on virtual dental cast analysis of 29 UCLP patients and 29 control individuals at the age of 15 years.

Sequential Shh expression in the development of the mouse upper functional incisor.

The mouse incisor is a frequently used model in studies of the molecular control of organ development. The appropriate interpretation of data on normogenesis is essential for understanding the data obtained in mutant mice. For this reason, we performed a very detailed investigation of the development of the upper incisor in wild-type mice from embryonic day (ED) 11.

The dynamics of supernumerary tooth development are differentially regulated by Sprouty genes.

In mice, a toothless diastema separates the single incisor from the three molars in each dental quadrant. In the prospective diastema of the embryo, small rudimentary buds are found that are presumed to be rudiments of suppressed teeth. A supernumerary tooth occurs in the diastema of adult mice carrying mutations in either Spry2 or Spry4.

Successful early neonatal repair of cleft lip within first 8 days of life.

Objective: In the children born with a cleft lip, surgery is the first step in correcting the inborn anomaly. In comparison with usually made 3-month surgery, benefits of the surgery in neonates have been reported: a very good wound healing, feeding facilitation, and good socialization of a child from neonatal age. The aims of the present study were to perform cheiloplasty in early newborns affected by the total cleft lip and palate (CLP) by the technique modified to search for optimum aesthetic result, and to assess the surgery outcome from qualitative and quantitative aspects.

Variability in palatal shape and size in patients with bilateral complete cleft lip and palate assessed using dense surface model construction and 3D geometric morphometrics.

Bilateral complete cleft lip and palate (BCLP) is the most severe of the common orofacial clefts and is associated with the greatest deformity during development. The aim of this study was to use geometric morphometrics to evaluate palatal shape and size variability in patients with BCLP in comparison to nonclefted Czech boys. The variability of palatal size and shape in BCLP patients was greater when compared with the nonclefted population.

Shh expression in a rudimentary tooth offers new insights into development of the mouse incisor.

For teeth as for any organ, knowledge of normal development is essential for the proper interpretation of developmental anomalies in mutant mice. It is generally accepted that tooth formation is initiated with a single signaling center that, in the incisor region, is exclusively related to the development of the functional adult incisor. Here, using a unique combination of computer-aided three-dimensional reconstructions and whole mount in situ hybridization of mandibles from finely staged wild-type mouse embryos, we demonstrate that several Sonic hedgehog (Shh) expression domains sequentially appear in the lower incisor region during early development.

Patterning by heritage in mouse molar row development.

It is known from paleontology studies that two premolars have been lost during mouse evolution. During mouse mandible development, two bud-like structures transiently form that may represent rudimentary precursors of the lost premolars. However, the interpretation of these structures and their significance for mouse molar development are highly controversial because of a lack of molecular data.

Revitalization of a diastemal tooth primordium in Spry2 null mice results from increased proliferation and decreased apoptosis.

An understanding of the factors that promote or inhibit tooth development is essential for designing biological tooth replacements. The embryonic mouse dentition provides an ideal system for studying such factors because it consists of two types of tooth primordia. One type of primordium will go on to form a functional tooth, whereas the other initiates development but arrests at or before the bud stage.

Temporal analysis of ectopic enamel production in incisors from sprouty mutant mice.

The mouse incisor has two unusual features: it grows continuously and it is covered by enamel exclusively on the labial side. The continuous growth is driven in part by epithelial stem cells in the cervical loop region that can both self-renew and give rise to ameloblasts. We have previously reported that ectopic enamel is found on the lingual side of the incisor in mice with loss-of-function of sprouty (spry) genes.

Chernobyl: relationship between the number of missing newborn boys and the level of radiation in the Czech regions.

Background: The number of newborn boys was higher than that of girls in the Czech Republic each month from 1950 to 2005. The only exception was November 1986, when the number of newborn boys was significantly reduced. This has been explained by a selective negative impact of the Chernobyl accident in April 1986 on male fetuses during the third month of their prenatal development.

An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors.

Rodent incisors grow throughout adult life, but are prevented from becoming excessively long by constant abrasion, which is facilitated by the absence of enamel on one side of the incisor. Here we report that loss-of-function of sprouty genes, which encode antagonists of receptor tyrosine kinase signaling, leads to bilateral enamel deposition, thus impeding incisor abrasion and resulting in unchecked tooth elongation. We demonstrate that sprouty genes function to ensure that enamel-producing ameloblasts are generated on only one side of the tooth by inhibiting the formation of ectopic ameloblasts from self-renewing stem cells, and that they do so by preventing the establishment of an epithelial-mesenchymal FGF signaling loop.

Disruption of the palatal rugae pattern in Tabby (eda) mutant mice.

The eda mouse gene is linked with anomalies of ectodermal derivatives, such as hair, glands, and teeth. The palatal rugae (oral mucosa foldings on the hard palate) are also ectodermal derivatives. Therefore, we searched for and compared palatal rugae anomalies of Tabby mice bearing a mutation in the eda gene with their wild-type counterparts.

Early development of the lower deciduous dentition and oral vestibule in human embryos.

The aim of this work was to investigate the early development of the deciduous dentition and oral vestibule in the human embryonic lower jaw. Histological sections and three-dimensional reconstructions from prenatal weeks 6-9 were used. A continuous anlage for the oral vestibule did not exist in the mandible.

Study of feasibility of the treatment with procainamide hydrochloride and cisplatin in pregnant mice.

Cisplatin is one of the most widely utilized anticancer drugs; nevertheless its use is often hampered by the onset of serious side effects. In spite of its tight binding to DNA, great teratogenic effects do not characterize cisplatin, although its embryolethal and growth retardation activities are quite remarkable. On the basis of our previous observations, demonstrating the usefulness of procainamide hydrochloride for the protection against cisplatin toxic effects in adult mice and rats, we now analyze the feasibility of the combined treatment with cisplatin and the antiarrhythmic drug procainamide hydrochloride in pregnant mice and the possible protective action of procainamide against the embryotoxic activity of cisplatin.

Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling.

Unlike humans, who have a continuous row of teeth, mice have only molars and incisors separated by a toothless region called a diastema. Although tooth buds form in the embryonic diastema, they regress and do not develop into teeth. Here, we identify members of the Sprouty (Spry) family, which encode negative feedback regulators of fibroblast growth factor (FGF) and other receptor tyrosine kinase signaling, as genes that repress diastema tooth development.

Phylogenetic memory of developing mammalian dentition.

Structures suppressed during evolution can be retraced due to atavisms and vestiges. Atavism is an exceptional emergence of an ancestral form in a living individual. In contrast, ancestral vestige regularly occurs in all members of an actual species.

Origin and developmental fate of vestigial tooth primordia in the upper diastema of the field vole (Microtus agrestis, Rodentia).

Objective: Odontogenesis in voles is a convenient model to test hypotheses on tooth development generated from investigations in the mouse. Similar to other rodents, the functional dentition of the vole includes a toothless diastema. At its mesial end, a vestigial tooth bud has been found in the upper jaw of vole embryos.