Since their recruitment in the oral cavity, approximately 450 million years ago, teeth have been subjected to strong selective constraints due to the crucial role that they play in species survival. It is therefore quite surprising that the ability to develop functional teeth has subsequently been lost several times, independently, in various lineages. In this review, we concentrate our attention on tetrapods, the only vertebrate lineage in which several clades lack functional teeth from birth to adulthood. Indeed, in other lineages, teeth can be absent in adults but be functionally present in larvae and juveniles, can be absent in the oral cavity but exist in the pharyngeal region, or can develop on the upper jaw but be absent on the lower jaw. Here, we analyse the current data on toothless (edentate) tetrapod taxa, including information available on enamel-less species. Firstly, we provide an analysis of the dispersed and fragmentary morphological data published on the various living taxa concerned (and their extinct relatives) with the aim of tracing the origin of tooth or enamel loss, i.e. toads in Lissamphibia, turtles and birds in Sauropsida, and baleen whales, pangolins, anteaters, sloths, armadillos and aardvark in Mammalia. Secondly, we present current hypotheses on the genetic basis of tooth loss in the chicken and thirdly, we try to answer the question of how these taxa have survived tooth loss given the crucial importance of this tool. The loss of teeth (or only enamel) in all of these taxa was not lethal because it was always preceded in evolution by the pre-adaptation of a secondary tool (beak, baleens, elongated adhesive tongues or hypselodonty) useful for improving efficiency in food uptake. The positive selection of such secondary tools would have led to relaxed functional constraints on teeth and would have later compensated for the loss of teeth. These hypotheses raise numerous questions that will hopefully be answered in the near future.

BackgroundOrodental diseases include several clinically and genetically heterogeneous disorders that can present in isolation or as part of a genetic syndrome. Due to the vast number of genes implicated in these disorders, establishing a molecular diagnosis can be challenging. We aimed to develop a targeted next-generation sequencing (NGS) assay to diagnose mutations and potentially identify novel genes mutated in this group of disorders.MethodsWe designed an NGS gene panel that targets 585 known and candidate genes in orodental disease. We screened a cohort of 101 unrelated patients without a molecular diagnosis referred to the Reference Centre for Oro-Dental Manifestations of Rare Diseases, Strasbourg, France, for a variety of orodental disorders including isolated and syndromic amelogenesis imperfecta (AI), isolated and syndromic selective tooth agenesis (STHAG), isolated and syndromic dentinogenesis imperfecta, isolated dentin dysplasia, otodental dysplasia and primary failure of tooth eruption.ResultsWe discovered 21 novel pathogenic variants and identified the causative mutation in 39 unrelated patients in known genes (overall diagnostic rate: 39%). Among the largest subcohorts of patients with isolated AI (50 unrelated patients) and isolated STHAG (21 unrelated patients), we had a definitive diagnosis in 14 (27%) and 15 cases (71%), respectively. Surprisingly, COL17A1 mutations accounted for the majority of autosomal-dominant AI cases.ConclusionsWe have developed a novel targeted NGS assay for the efficient molecular diagnosis of a wide variety of orodental diseases. Furthermore, our panel will contribute to better understanding the contribution of these genes to orodental disease.Trial registration numbersNCT01746121 and NCT02397824.

The present study focuses on the main characteristics of first-generation teeth (i.e., the first teeth of the dentition to develop in a given position and to become functional) in representatives of the major lineages of nonmammalian vertebrates (chondrichthyans, actinopterygians, and sarcopterygians: dipnoans, urodeles, squamates, and crocodiles). Comparative investigations on the LM and TEM level reveal the existence of two major types of first-generation teeth. One type (generalized Type 1) is characterized by its small size, conical shape, atubular dentine, and small pulp cavity without capillaries and blood vessels. This type is found in actinopterygians, dipnoans, and urodeles and coincides with the occurrence of short embryonic periods in these species. The other type assembles a variety of first-generation teeth, which have in common that they represent miniature versions of adult teeth. They are generally larger than the first type, have more complex shapes, tubular dentine, and a large pulp cavity containing blood vessels. These teeth are found in chondrichtyans, squamates, and crocodiles, taxa which all share an extended embryonic period. The presence in certain taxa of a particular type of first-generation teeth is neither linked to their phylogenetic relationships nor to adult body size or tooth structure, but relates to the duration of embryonic development. Given that the plesiomorphic state in vertebrates is a short embryonic development, we consider the generalized Type 1 first-generation tooth to represent an ancestral character for gnathostomes. We hypothesize that an extended embryonic development leads to the suppression of tooth generations in the development of dentition. These may still be present in the form of rudimentary germs in the embryonic period. In our view, this generalized Type 1 first-generation teeth has been conserved through evolution because it represents a very economic and efficient way of building small and simple teeth adapted to larval life. The highly adapted adult dentition characteristic for each lineage has been possible only through polyphyodonty.