(1/272) Dosage requirement of Pitx2 for development of multiple organs.

Pitx2 is a homeodomain transcription factor that is mutated in Rieger syndrome, a haploinsufficiency disorder affecting eyes and teeth. Pitx2 also has a postulated role in left-right axis determination. We assessed the requirements for Pitx2 directly by generating hypomorphic and null alleles. Heterozygotes for either allele have eye abnormalities consistent with Rieger syndrome. The ventral body wall fails to close in embryos homozygous for the null allele, leaving the heart and abdominal organs externalized and the body axis contorted. In homozygotes for either allele, the heart tube undergoes normal, rightward looping and the stomach is positioned normally. In contrast, homozygotes for both alleles exhibit right isomerization of the lungs. Thus, Pitx2 is required for left-right asymmetry of the lungs but not other organs. Homozygotes for either allele exhibit septal and valve defects, and null homozygotes have a single atrium proving that a threshold level of Pitx2 is required for normal heart development. Null homozygotes exhibit arrest of pituitary gland development at the committed Rathke pouch stage and eye defects including optic nerve coloboma and absence of ocular muscles. This allelic series establishes that Pitx2 is required for the development of mulitple organs in a dosage-sensitive manner.  (+info)

(2/272) Cre-mediated gene inactivation demonstrates that FGF8 is required for cell survival and patterning of the first branchial arch.

In mammals, the first branchial arch (BA1) develops into a number of craniofacial skeletal elements including the jaws and teeth. Outgrowth and patterning of BA1 during early embryogenesis is thought to be controlled by signals from its covering ectoderm. Here we used Cre/loxP technology to inactivate the mouse Fgf8 gene in this ectoderm and have obtained genetic evidence that FGF8 has a dual function in BA1: it promotes mesenchymal cell survival and induces a developmental program required for BA1 morphogenesis. Newborn mutants lack most BA1-derived structures except those that develop from the distal-most region of BA1, including lower incisors. The data suggest that the BA1 primordium is specified into a large proximal region that is controlled by FGF8, and a small distal region that depends on other signaling molecules for its outgrowth and patterning. Because the mutant mice resemble humans with first arch syndromes that include agnathia, our results raise the possibility that some of these syndromes are caused by mutations that affect FGF8 signaling in BA1 ectoderm.  (+info)

(3/272) Dental manifestations in severe combined immunodeficiency following bone marrow transplantation.

Severe combined immunodeficiency (SCID) is a rare primary immunodeficiency disorder with an estimated overall frequency of 1 in 75 000 live births. Bone marrow transplantation is the only curative treatment available. Using T cell-depleted HLA non-identical bone marrow requires preconditioning with a short course of cytotoxic chemotherapy. We report severe dental developmental anomalies in three such patients under long-term follow up.  (+info)

(4/272) Sonic hedgehog regulates growth and morphogenesis of the tooth.

During mammalian tooth development, the oral ectoderm and mesenchyme coordinate their growth and differentiation to give rise to organs with precise shapes, sizes and functions. The initial ingrowth of the dental epithelium and its associated dental mesenchyme gives rise to the tooth bud. Next, the epithelial component folds to give the tooth its shape. Coincident with this process, adjacent epithelial and mesenchymal cells differentiate into enamel-secreting ameloblasts and dentin-secreting odontoblasts, respectively. Growth, morphogenesis and differentiation of the epithelium and mesenchyme are coordinated by secreted signaling proteins. Sonic hedgehog (Shh) encodes a signaling peptide which is present in the oral epithelium prior to invagination and in the tooth epithelium throughout its development. We have addressed the role of Shh in the developing tooth in mouse by using a conditional allele to remove Shh activity shortly after ingrowth of the dental epithelium. Reduction and then loss of Shh function results in a cap stage tooth rudiment in which the morphology is severely disrupted. The overall size of the tooth is reduced and both the lingual epithelial invagination and the dental cord are absent. However, the enamel knot, a putative organizer of crown formation, is present and expresses Fgf4, Wnt10b, Bmp2 and Lef1, as in the wild type. At birth, the size and the shape of the teeth are severely affected and the polarity and organization of the ameloblast and odontoblast layers is disrupted. However, both dentin- and enamel-specific markers are expressed and a large amount of tooth-specific extracellular matrix is produced. This observation was confirmed by grafting studies in which tooth rudiments were cultured for several days under kidney capsules. Under these conditions, both enamel and dentin were deposited even though the enamel and dentin layers remained disorganized. These studies demonstrate that Shh regulates growth and determines the shape of the tooth. However, Shh signaling is not essential for differentiation of ameloblasts or odontoblasts.  (+info)

(5/272) The Class II Division 2 craniofacial type is associated with numerous congenital tooth anomalies.

The aim of the present study was to examine whether a putative relationship exists between the Class II division 2 craniofacial type and congenital anomalies of the dentition, such as missing teeth, peg-shaped laterals, transpositions, supernumerary teeth and canine impactions. Two hundred and sixty-seven untreated patients with Class II division 2 malocclusion were examined. The results show that 56.6 per cent of the patients exhibited some form of congenital tooth anomaly, 13.9 per cent agenesis of the upper lateral incisors, 7.5 per cent peg-shaped upper laterals, while impacted canines were present in 33.5 per cent of the subjects. Transpositions were present in 1.1 per cent of the patients and in all cases the canine was involved. No patient exhibited a supernumerary tooth. Comparing the results of the present study with existing data on the percentage of congenital tooth anomalies in the general population, it can be concluded that Class II division 2 malocclusions are closely associated with congenital tooth anomalies.  (+info)

(6/272) A radiographic comparison of apical root resorption after orthodontic treatment with a standard edgewise and a straight-wire edgewise technique.

The purpose of this study was to compare the severity of apical root resorption occurring in patients treated with a standard edgewise and a straight-wire edgewise technique, and to assess the influence of known risk factors on root resorption incident to orthodontic treatment. The sample consisted of 80 patients with Angle Class II division 1 malocclusions, treated with extraction of at least two maxillary first premolars. Variables recorded for each patient included gender, age, ANB angle, overjet, overbite, trauma, habits, invagination, agenesis, tooth shedding, treatment duration, use of Class II elastics, body-build, general factors, impacted canines, and root form deviation. Forty patients were treated with a standard edgewise and 40 with a straight-wire edgewise technique, both with 0.018-inch slot brackets. Crown and root lengths of the maxillary incisors were measured on pre- and post-treatment periapical radiographs corrected for image distortion. Percentage of root shortening and root length loss in millimetres were then calculated. There was significantly more apical root resorption (P < 0.05) of both central incisors in the standard than in the straight-wire edgewise group. No significant difference was found for the lateral incisors. Root shortening of the lateral incisors was significantly associated with age, agenesis, duration of contraction period (distalization of incisors), and invagination, while root shortening of the central incisors was related to treatment group and trauma.  (+info)

(7/272) Tooth discolouration and staining: a review of the literature.

OBJECTIVE: To carry out an extensive review of the literature on tooth staining with particular regard to some of the more recent literature on the mechanisms of tooth staining involving mouthrinses. DESIGN: Comprehensive review of the literature over four decades. CONCLUSIONS: A knowledge of the aetiology of tooth staining is of importance to dental surgeons in order to enable a correct diagnosis to be made when examining a discoloured dentition and allows the dental practitioner to explain to the patient the exact nature of the condition. In some instances, the mechanism of staining may have an effect on the outcome of treatment and influence the treatment options the dentist will be able to offer to patients.  (+info)

(8/272) Congenital tooth anomalies and malocclusions: a genetic link?

The aim of the present study was to investigate putative relationships between different malocclusions such as Class III and Class II division 1, and congenital tooth anomalies. Two-hundred Class III and 215 Class II division 1 patients were examined for the presence of any of the following congenital tooth anomalies: maxillary incisor hypodontia, maxillary canine impaction, transpositions, supernumerary teeth, and tooth agenesis. Their occurrence rates were then calculated as a percentage of the total sample and were compared for statistical differences. The results revealed no statistical difference (P > 0.05) in the occurrence rates of upper lateral incisor agenesis, peg-shaped laterals, impacted canines, or supernumerary teeth between the Class III and the Class II division 1 malocclusions. When the occurrence rate of all congenital tooth anomalies was compared between the two malocclusions, Class III subjects showed significantly higher rates (P < 0.05). Comparison with published surveys on general populations showed similar occurrence rates. It can be concluded that subjects with Class III and Class II division 1 malocclusions show patterns of congenital tooth anomalies similar to those observed in the general population. Congenital tooth anomalies may represent another criterion for the study of malocclusion, with respect to their origin and development.  (+info)