Abstract

Human dental development is characterized by formation of primary teeth, which are subsequently replaced by the secondary dentition. The secondary dentition consists of incisors, canines, and premolars, which are derived from the successional dental lamina of the corresponding primary tooth germs; and molar teeth, which develop as a continuation of the dental lamina. Currently, very little is known about the molecular regulation of human successional tooth formation. Here, we have investigated expression of three candidate regulators for human successional tooth formation; the Fibroblast Growth Factor-antagonist SPROUTY2, the Hedgehog co-receptor GAS1 and the RUNT-related transcription factor RUNX2. At around 8 weeks of development, only SPROUTY2 showed strong expression in both epithelium and mesenchyme of the early bud. During the cap stage between 12–14 weeks, SPROUTY2 predominated in the dental papilla and inner enamel epithelium of the developing tooth. No specific expression was seen in the successional dental lamina. GAS1 was expressed in dental papilla and follicle, and associated with mesenchyme adjacent to the primary dental lamina during the late cap stage. In addition, GAS1 was identifiable in mesenchyme adjacent to the successional lamina, particularly in the developing primary first molar. For RUNX2, expression predominated in the dental papilla and follicle. Localized expression was seen in mesenchyme adjacent to the primary dental lamina at the late cap stage; but surprisingly, not in the early successional lamina at these stages. These findings confirm that SPROUTY2, GAS1, and RUNX2 are all expressed during early human tooth development. The domains of GAS1 and RUNX2 are consistent with a role influencing function of the primary dental lamina but only GAS1 transcripts were identifiable in the successional lamina at these early stages of development.

Highlights

  • Vertebrates demonstrate wide variation in the functional requirements of their masticatory systems and this is reflected in the anatomic variation within their dentitions

  • In many mammals, including humans and other primates, the transition from a primary to permanent dentition is achieved through the generation of successional incisor, canine and premolar teeth, which are derived from a successional dental lamina that forms on the lingual side of the corresponding primary tooth germ (Berkovitz et al, 2009; Ten Cate, 2014)

  • The mandibular primary lateral incisor (Figure 1B), primary canine (Figure 1C) and primary first and second molar (Figures 1D,E) tooth germs were present, appearing further posteriorly in each respective quadrant of the mandible. These teeth were all at the cap stage of development, with the early successional dental laminae associated with the permanent tooth germs visible (Figures 1D,E)

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Summary

Introduction

Vertebrates demonstrate wide variation in the functional requirements of their masticatory systems and this is reflected in the anatomic variation within their dentitions. The mammalian dentition is classically heterodont, with incisor, canine, and molariform teeth present in both the primary and secondary dentitions. In many mammals, including humans and other primates, the transition from a primary to permanent dentition is achieved through the generation of successional incisor, canine and premolar teeth, which are derived from a successional dental lamina that forms on the lingual side of the corresponding primary tooth germ (Berkovitz et al, 2009; Ten Cate, 2014). The secondary molar dentition is accessional, the first molar initiating from a posterior extension of the primary dental lamina and subsequent molars budding off through a process termed serial addition (Juuri et al, 2013)

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