Expression of Dlx genes during the development of the zebrafish pharyngeal dentition: evolutionary implications

Abstract

In order to investigate similarities and differences in genetic control of development among teeth within and between species, we determined the expression pattern of all eight Dlx genes of the zebrafish during development of the pharyngeal dentition and compared these data with that reported for mouse molar tooth development. We found that (i) dlx1a and dlx6a are not expressed in teeth, in contrast to their murine orthologs, Dlx1 and Dlx6; (ii) the expression of the six other zebrafish Dlx genes overlaps in time and space, particularly during early morphogenesis; (iii) teeth in different locations and generations within the zebrafish dentition differ in the number of genes expressed; (iv) expression similarities and differences between zebrafish Dlx genes do not clearly follow phylogenetic and linkage relationships; and (v) similarities and differences exist in the expression of zebrafish and mouse Dlx orthologs. Taken together, these results indicate that the Dlx gene family, despite having been involved in vertebrate tooth development for over 400 million years, has undergone extensive diversification of expression of individual genes both within and between dentitions. The latter type of difference may reflect the highly specialized dentition of the mouse relative to that of the zebrafish, and/or genome duplication in the zebrafish lineage facilitating a redistribution of Dlx gene function during odontogenesis.

Transgenic analysis of Dlx regulation in fish tooth development reveals evolutionary retention of enhancer function despite organ loss

“…Some of these changes might involve other members of the Dlx gene family. Eight Dlx genes are present in the zebrafish (35) and six of these are expressed in zebrafish pharyngeal teeth, with considerable spatial and temporal overlap (20). Redundancy of Dlx function has been documented in mammals (36), and our finding that increasingly severe phenotypes are produced by knocking down combinations of Dlx genes (Fig.…”

“…5) suggests redundancy in the teleost dentition as well. Interestingly, despite the expression of Dlx genes during zebrafish pharyngeal tooth initiation (20) and the fact that dlx2b prefigures the epithelium from which oral teeth arise in A. mexicanus (19), none of the phenotypes we obtained from gene knockdown involved the early arrest of tooth initiation, as seen in the mouse (22). This result might be explained by the more extensive redundancy of Dlx gene expression during tooth initiation in the zebrafish relative to the mouse (20).…”

“…Interestingly, despite the expression of Dlx genes during zebrafish pharyngeal tooth initiation (20) and the fact that dlx2b prefigures the epithelium from which oral teeth arise in A. mexicanus (19), none of the phenotypes we obtained from gene knockdown involved the early arrest of tooth initiation, as seen in the mouse (22). This result might be explained by the more extensive redundancy of Dlx gene expression during tooth initiation in the zebrafish relative to the mouse (20). Alternatively, because the doses of MOs we used had to be adjusted to allow the larvae to develop to the ages at which teeth appear, we are likely to have produced only partial losses of function.…”

“…19). Dlx genes are expressed at numerous stages of tooth development in the zebrafish (20) and the mouse (21), and loss of Dlx function leads to early arrest of tooth development in the mouse (22). We have argued previously that Dlx genes are likely downstream of the cause of cypriniform oral tooth loss (19) and are thus a good model for the fate of developmental pathways once an initiation signal has been modified in evolution.…”

Expression of the dlx gene family during formation of the cranial bones in the zebrafish (Danio rerio): Differential involvement in the visceral skeleton and braincase

“…These bones (dermal and perichondral bones) lie in the close vicinity of the epithelium, very near to the basal lamina. Epithelial expression of dlx genes is not unusual in se, and several studies have reported the epithelial expression (Ekker et al, 1992;Akimenko et al, 1994;Ellies et al, 1997;Solomon and Fritz, 2002;Borday-Birraux et al, 2006). Sites of epithelial-mesenchymal signaling are known to be the sites of dlx expression for vertebrates (Stock et al, 1996).…”