Figure 7. Comparative models of cellular and molecular processes controlling oral tooth replacement in polyphyodont species.

Schematic drawings of oral tooth replacement strategies in polyphyodont species with molecularly-characterized LRC populations: spotted catshark (Martin et al., 2016), pufferfish (Thiery et al., 2017), Atlantic salmon (Vandenplas et al., 2016), African bichir (Vandenplas et al., 2016), bearded dragon pleurodont and acrodont teeth (this study), leopard gecko (Handrigan et al., 2010), and American alligator (Wu et al., 2013). The putative stem cell niche of monophyodont mouse incisor (Harada et al., 1999) is also shown for comparison. In spotted catshark, SOX2-positive putative dental progenitors migrate from the superficial taste/tooth junction (T/TJ) towards the successional dental lamina (SDL). In pufferfish but also cichlid fish (Fraser et al., 2013), a SOX2-positive putative dental progenitor niche resides in the most superficial dental lamina (DL). In Atlantic salmon and African bichir, no epithelial LRCs have been identified despite positive SOX2 expression in the OE and outer dental epithelium transition zone. In the leopard gecko, LRCs expressing adult stem cell markers such as IGFBP5 and LGR5 reside on the lingual side of the DL. In the American alligator, putative stem cells localize to the distal enlarged bulge of the DL. In both leopard gecko and American alligator, SOX2 expression has been shown to overlap with the epithelial region containing putative stem cells (Juuri et al., 2013), but no co-localization studies are available. In mouse incisors, SOX2-positive putative stem cells responsible for continual growth are located in the labial cervical loop (LaCL; Juuri et al., 2012). In bearded dragon pleurodont teeth, LRCs are located both in the SOX2-positive oral epithelium (OE; region similar to the T/TJ) and IGFBP5/LGR5/SOX2-positive DDL (region similar to the gecko DL). During regeneration, cells migrate from the superficial OE towards the SDL, the SDL shows focal expression of SDL marker genes (PITX2/LEF1), and both the SDL and surrounding mesenchyme exhibit relatively high expression of newly identified dental genes (ALX1/SIX3/ISL1), thus leading to the initiation of replacement tooth. In acrodont teeth, LRCs are also evident in the SOX2-positive OE and cell migration occurs from the superficial OE towards the SDL, thus contributing to SDL growth. However, the acrodont SDL shows scattered expression of SDL markers and low expression of newly identified dental genes, most likely as a result of absence of DL stem/progenitor cells and SDL organization, and no replacement teeth are formed.