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Teeth and Genes Teeth and dentition Human dentition consists of 20 deciduous teeth and 32 permanent teeth. Deciduous teeth are shed during childhood to give way for the permanent teeth. Replacement of teeth is common among animals. However, it does not happen in the commonly used laboratory animal, the mouse. Mouse has 16 teeth which serve it for whole of its life. Different types of teeth are classified according to their position and shape. The tooth series in each jaw and on both sides ("quadrants") are the same even though the shapes of individual teeth in the jaws vary. Incisors (two in each quadrant) and canines (one in each quadrant) are the front teeth. Premolars (two in each quadrant) and molars (three in each quadrant) are the posterior teeth. Deciduous dentition has no premolars and only two molars in each guadrant. Mouse has only one incisor in each quadrant, and behind a gap ("diastema"), three molars. Many dentists have been researching into the genes involved in tooth development. Related Article HOW DO TEETH DEVELOP • The basic development of all teeth happens in the same way and bears similarities to the development of many other epithelial appendages like hair, glands, and limbs (see illustrations). In embryo, oral epithelial cells (or cells of the epithelial dental lamina) grow into the underlying mesenchymal tissue. Subsequently, the epithelial compartment, the enamel organ, and the mesenchymal tissues, the dental papilla and the dental follicle, grow and form the final shape of the tooth ("morphogenesis"). Different stages of tooth development are called the bud, cap or bell stages according to the shape of the tooth germ. Mesenchymal cells of the dental papilla that are adjacent to the enamel organ, differentiate to odontoblasts and start to secrete dentin, the inner hard tissue of teeth. Epithelial cells adjacent to differentiating odontoblasts differentiate to ameloblasts, and secrete enamel, the outer cover of teeth. Finally the roots develop and the tooth erupts into the oral cavity. Secondary teeth are formed in the similar fashion, but the development happens very slowly. HOW IS TEETH DEVELOPMENT REGULATED • Research has shown that tooth development is regulated by interactions of the epithelial and mesenchymal tissues. The tissues interact reciprocally, sending signals to each other. These signals are most often small proteins that are secreted by one tissue and received by another. The cells interpretation of a received signals then determines its response, growth, gene expression or even cell death. It is obvious that there are subtle differences of these signals during development of different teeth. Similar signals and responses are used during development of many organs. GENES IN TOOTH DEVELOPMENT • Scientists all over the world study expression of different genes during development. The existing knowledge of genes expressed during tooth development has been collected to a WWWdatabase, Gene expression in tooth. The functions of genes are studied by using laboratory animals (mouse and rat) or looking for gene defects that cause abnormal tooth development in humans. CONGENITALLY MISSING TEETH • Missing of one or more teeth is perhaps our most common congenital malformation. More than 20 % of us lack one or more wisdom teeth (third molars). More than five percent of us lack one or more second premolars or upper second (lateral) incisors. Lack of a large amount of teeth, though, is much more rare. • Hypodontia refers to congenital lack of a few teeth. The population frequency is over 5 % (missing of wisdom teeth not included) • Oligodontia refers to congenital lack of more than six teeth (wisdom teeth not included). The population frequency is low, especially for cases when absence of teeth is the only malformation ("isolated" cases). Most often oligodontia appears as part of some congenital syndrome that affects several organ systems. These include • • • • • ectodermal dysplasias, i.e. defects of skin, hair, nails, teeth and ectodermal glands oral clefting (cleft lip, cleft palate, or cleft lip and palate) Rieger syndrome, Char syndrome etc Anodontia refers to complete lack of teeth, which is very rare. Tooth agenesis, also used as partial or selective tooth agenesis, may refer to all of the above. CAUSES OF CONGENITALLY MISSING TEETH • Several environmental factors like virus infections, toxins and radio- or chemotherapy may cause missing of permanent teeth. However, most of the cases are caused by genetic factors. The heritability of congenitally missing teeth has been shown in many studies. The genetic factors may be dominant or recessive and it is obvious that in many cases multiple genetic (and environmental) factors are acting together. The importance of genetic factors is shown by appearance of multiple cases among relatives (familial clustering) and higher concordance in identical than in non-identical twins. • Dominant inheritance of congenitally missing teeth has been shown both in hypodontia and oligodontia. However in both cases the amount and identity of missing teeth may vary between relatives. In hypodontia, the variability may extend to no teeth actually missing ("reduced penetrance"). The variability is probably caused by other genetic and environmental factors, and in some cases the etiology is analogous to multifactorial traits. • An example of recessive inheritance is given by recessive incisor hypodontia (RIH). In this condition described by us, a recessive gene causes congenital missing of several incisors, including lower permanent incisors and often decidusous incisors, too) the inheritance is recessive. GENES FOR CONGENITALLY MISSING TEETH • We already know several genes which, when defective, cause congenitally missing teeth. The known gene defects include mostly those that cause a multi-organ syndrome (genes EDA, EDAR, EDARADD, IKKgamma, p63, IRF6, PITX2, TFAPB2, SHH, OFD1). Only two genes are known so far where defects cause isolated tooth agenesis. Dominant loss-of function mutations in MSX1 and PAX9 cause oligodontia. Identication of gene defects that cause isolated hypodontia, the most common type of congenitally missing teeth, has been much more difficult. I IMAGES INVOLVED IN TOOTH DEVELOMENT IMAGES OF GENE INVOLVED IN TOOTH DEVELOPMENT ABNORMALITIES OF TOOTH DEVELOPMENT • Numerous genetic and environmental factors may cause abnormalities in tooth development. These may include • defects of structure (e.g. abnormal enamel, amelogenesis imperfecta, or abnormal dentin, dentinogenesis imperfecta or dentin dysplasia) • abnormal position of tooth • reduced size and abnormal shape of teeth (e.g. "peg-shaped" incisors, taurodontism, or short root anomaly) • missing of one or more teeth (hypodontia, oligodontia, tooth agenesis).