Conservation and divergence of Bmp2a, Bmp2b, and Bmp4 expression patterns within and between dentitions of teleost fishes

Abstract

The diversity of tooth location in teleost fishes provides an excellent system for comparing genetic divergence between teeth in different species (phylogenetic homologs) with divergence between teeth within one species (iterative homologs). We have chosen to examine the expression of three members of the bone morphogenetic protein (Bmp) family because they are known to play multiple roles in tooth development and evolution in tetrapod vertebrates. We characterized expression of Bmp2a, Bmp2b, and Bmp4 during the development of oral and pharyngeal dentitions in three species of teleost fishes, the zebrafish (Danio rerio), Mexican tetra (Astyanax mexicanus), and Japanese medaka (Oryzias latipes). We found that expression in teleosts is generally highly conserved, with minor differences found among both iteratively homologous and phylogenetically homologous teeth. Expression of orthologous genes differs in several ways between the teeth of teleost fishes and those of the mouse, but between these vertebrate groups the summed expression pattern of Bmp genes is highly conserved. Significantly, the toothless oral region of the zebrafish lacks Bmp expression domains found in teleosts with oral teeth, implicating these genes in evolutionary tooth loss. We conclude that Bmp expression has been largely conserved in vertebrate tooth development over evolutionary time, and that loss of Bmp expression is correlated with region-specific loss of the dentition in a major group of fishes.

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

“…Wise and Stock (14) found that loss of oral bmp2b expression is associated with cypriniform oral tooth loss. Dlx2 expression is known to be regulated by Bmp4 in mouse tooth development (15), but whether dental Dlx2b expression in teleosts is regulated by Bmp2b remains to be determined.…”

“…This pattern suggests that failure to regain oral teeth is not the result of an absence of selection for their function. The specific genetic changes that caused loss of cypriniform oral teeth remain unknown (14,19). If our finding that Dlx2b retains the capacity for expression in oral teeth is representative of the genetic pathways controlling tooth development, it is possible that the redeployment or modification of one or a few upstream signals could restore oral teeth.…”

“…molars and incisors; ref. 11) and between oral and pharyngeal teeth of fishes (12)(13)(14) show extensive similarities in the genes involved in their development. Where differences in expression between different types of developing teeth have been documented, these involve genes that participate in the development of other organs.…”

Selection and constraint underlie irreversibility of tooth loss in cypriniform fishes

“…3 A and E) and a variety of tooth germ markers (Fig. S4) that have been shown to differ in their expression between wild-type zebrafish and A. mexicanus (21,32). We therefore asked whether the oral epithelium is competent to respond to Eda.…”

“…Probes for A. mexicanus bmp2a, bmp2b, dlx2b, pitx2, and shh were as previously described (21,32). A. mexicanus edar and edaradd probes correspond to the positions listed for their zebrafish orthologs, and the eda and fgf4 probes for this species comprised the regions corresponding to zebrafish positions 769-1151 (NM_001115064) and 538-887 (NM_131635.2), respectively.…”