Early Regression of the Dental Lamina Underlies the Development of Diphyodont Dentitions

Abstract

Functional tooth germs in mammals, reptiles, and chondrichthyans are initiated from a dental lamina. The longevity of the lamina plays a role in governing the number of tooth generations. Monophyodont species have no replacement dental lamina, while polyphyodont species have a permanent continuous lamina. In diphyodont species, the dental lamina fragments and regresses after initiation of the second tooth generation. Regression of the lamina seems to be an important mechanism in preventing the further development of replacement teeth. Defects in the complete removal of the lamina lead to cyst formation and has been linked to ameloblastomas. Here, we show the previously unknown mechanisms behind the disappearance of the dental lamina, involving a combination of cell migration, cell-fate transformation, and apoptosis. Lamina regression starts with the loss of the basement membrane, allowing the epithelial cells to break away from the lamina and migrate into the surrounding mesenchyme. Cells deactivate epithelial markers (E-cadherin, cytokeratin), up-regulate Slug and MMP2, and activate mesenchymal markers (vimentin), while residual lamina cells are removed by apoptosis. The uncovering of the processes behind lamina degradation allows us to clarify the evolution of diphyodonty, and provides a mechanism for future manipulation of the number of tooth generations.

Spatially restricted dental regeneration drives pufferfish beak development

“…In polyphyodont species the dental lamina must be regulated and maintained to support the production of further tooth generations (34). Pufferfishes form their teeth intraosseously and develop a dentition entirely confluent with the supporting jaw-bone, raising the question of where epithelial dental progenitors reside in a system in which the developing dentition has become spatially separated from the oral epithelium.…”

Evolution and developmental diversity of tooth regeneration

“…In species that only have one set of teeth the successional lamina forms but stops proliferating, losing its bulge shape. At the same time apoptosis is upregulated at the end of the lamina [44,55,57]. Interestingly loss of the successional lamina, and therefore the ability to make a second generation of teeth, is associated with the timing of fusion of the functional tooth with the surrounding bone [44].…”

“…This part of the lamina has been proposed to contain the dental epithelial stem cells and this breakdown may result in loss of the cells that would normally make the next tooth, or alternatively break down could be a consequence of loss of odontogenic potential in this region. In the mini-pig the loss of the dental lamina appears to involve a mix of apoptosis and transformation of the epithelial lamina cells to a mesenchymal fate [57]. Failure for the lamina to break down completely has been proposed to be the cause of epithelial pearls, which can lead to cysts and tumours [63,65].…”

“…The source of epithelial cells necessary for replacing teeth, in most toothed vertebrates, appears to be the dental lamina [10,12,14,28,30,33,46,57,62]. The early odontogenic band provides genetic cues that support a dental fate and the patterning of tooth units from these epithelial cells.…”

Aging of perennial cells and organ parts according to the programmed aging paradigm

“…A species is defined as monophyodont, diphyodont, or polyphyodont when in its life cycle it has one, two, or many successive sets of teeth, respectively (Buchtova et al 2012). In our species, which is diphyodont, a set of deciduous teeth (milk teeth) is replaced by a new set of permanent (adult) teeth, which has no subsequent turnover.…”