We present direct evidence of an activator-inhibitor system in the generation of the regularly spaced transverse ridges of the palate. We show that new ridges, or rugae, marked by stripes of Sonic hedgehog (Shh) expression, appear at two growth zones where the space between previously laid-down rugae increases. However, inter-rugal growth is not absolutely required: new stripes still appear when growth is inhibited. Furthermore, when a ruga is excised new Shh expression appears, not at the cut edge but as bifurcating stripes branching from the neighbouring Shh stripe, diagnostic of a Turing-type reaction-diffusion mechanism. Genetic and inhibitor experiments identify Fibroblast Growth Factor (FGF) and Shh as an activator-inhibitor pair in this system. These findings demonstrate a reaction-diffusion mechanism likely to be widely relevant in vertebrate development.
Clefts of the lip and palate are a common craniofacial anomaly, requiring complex multidisciplinary treatment and having lifelong implications for affected individuals. The aetiology of both cleft lip with or without cleft palate (CLP) and isolated cleft palate (CP) is thought to be multifactorial, with both genetic and environmental factors playing a role. In recent years, a number of significant breakthroughs have occurred with respect to the genetics of these conditions, in particular, characterization of the underlying gene defects associated with several important clefting syndromes. These include the identification of mutations in the interferon regulatory factor-6 (IRF6) gene as the cause of van der Woude syndrome and the poliovirus receptor related-1 (PVRL1) gene as being responsible for an autosomal recessive ectodermal dysplasia syndrome associated with clefting. While no specific disease-causing gene mutations have been identified in non-syndromic clefting, a number of candidate genes have been isolated through both linkage and association studies. However, it is clear that environmental factors also play a role and an important area of future research will be to unravel interactions that occur between candidate genes and environmental factors during early development of the embryo. Orthodontists are intimately involved in the therapeutic management of individuals affected by CLP and it is important that they keep abreast of current knowledge of the aetiology behind these conditions. This review aims to summarize some of the more significant advances in the genetics of CLP and highlight current thinking on the modes of inheritance and genetic loci that might be involved in this complex disorder.
The aim of this study was to compare the degree of discomfort experienced during the period of initial orthodontic tooth movement using Damon3 self-ligating and Synthesis conventional ligating pre-adjusted bracket systems. Sixty-two subjects were recruited from two centres (32 males and 30 females; mean age 16 years, 3 months) with lower incisor irregularity between 5 and 12 mm and a prescribed extraction pattern, including lower first premolar teeth. These subjects were randomly allocated for treatment with either bracket system. Fully ligated Damon3 0.014-inch Cu NiTi archwires were used for initial alignment in both groups. Following archwire insertion, the subjects were given a prepared discomfort diary to complete over the first week, recording discomfort by means of a 100 mm visual analogue scale at 4 hours, 24 hours, 3 days, and 1 week. The subjects also noted any self-prescribed analgesics that were taken during the period of observation. Data were analysed using repeated measures analysis of variance. There were no statistically significant differences in perceived discomfort levels between the two appliances; discomfort did not differ at the first time point and did not develop differently across subsequent measurement times. Overall, this investigation found no evidence to suggest that Damon3 self-ligating brackets are associated with less discomfort than conventional pre-adjusted brackets during initial tooth alignment, regardless of age or gender.
This article summarises recently updated guidelines produced by the Clinical Governance Directorate of the British Orthodontic Society through the Clinical Standards Committee of the Faculty of Dental Surgery, Royal College of Surgeons of England (FDSRCS) on the extraction of first permanent molars in children. The first permanent molar is susceptible to chronological enamel defects, molar-incisor hypomineralisation and caries, which may necessitate enforced extraction in the developing dentition. In the right circumstances, the extraction of these teeth can be followed by successful eruption of the second permanent molar and ultimately, third molar eruption to complete the molar dentition. For this reason, elective extraction of first permanent molars with a questionable long-term prognosis should be considered when planning enforced extractions. However, a number of factors can influence the decision-making process, including the necessity for a general anaesthetic to allow extraction, potential cooperation with restorative or orthodontic treatment and likely future preventative practice within the family. Moreover, the presence of any underlying malocclusion also needs to be evaluated within the context of extraction planning. The current available evidence has been evaluated and awarded a grade based upon those recommended by the Scottish Intercollegiate Guidelines Network.
Holoprosencephaly (HPE) is a clinically heterogeneous developmental anomaly affecting the CNS and face, in which the embryonic forebrain fails to divide into distinct halves. Numerous genetic loci and environmental factors are implicated in HPE, but mutation in the sonic hedgehog (Shh) gene is an established cause in both humans and mice. As growth arrest-specific 1 (Gas1) encodes a membrane glycoprotein previously identified as a Shh antagonist in the somite, we analyzed the craniofacial phenotype of mice harboring a targeted Gas1 deletion. Gas1 -/-mice exhibited microform HPE, including midfacial hypoplasia, premaxillary incisor fusion, and cleft palate, in addition to severe ear defects; however, gross integrity of the forebrain remained intact. These defects were associated with partial loss of Shh signaling in cells at a distance from the source of transcription, suggesting that Gas1 can potentiate hedgehog signaling in the early face. Loss of a single Shh allele in a Gas1 -/-background significantly exacerbated the midline craniofacial phenotype, providing genetic evidence that Shh and Gas1 interact. As human GAS1 maps to chromosome 9q21.3-q22, a region previously associated with nonsyndromic cleft palate and congenital deafness, our results establish GAS1 as a potential locus for several human craniofacial malformations.
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