The evolution of the vertebrate Dlx gene family.

Abstract

The vertebrate Dlx gene family consists of homeobox-containing transcription factors distributed in pairs on the same chromosomes as the Hox genes. To investigate the evolutionary history of Dlx genes, we have cloned five new zebrafish family members and have provided additional sequence information for two mouse genes. Phylogenetic analyses of Dlx gene sequences considered in the context of their chromosomal arrangements suggest that an initial tandem duplication produced a linked pair of Dlx genes after the divergence of chordates and arthropods but prior to the divergence of tunicates and vertebrates. This pair of Dlx genes was then duplicated in the chromosomal events that led to the four clusters of Hox genes characteristic of bony fish and tetrapods. It is possible that a pair of Dlx genes linked to the Hoxc cluster has been lost from mammals. We were unable to distinguish between independent duplication and retention of the ancestral state of bony vertebrates to explain the presence of a greater number of Dlx genes in zebrafish than mammals. Determination of the linkage relationship of these additional zebrafish Dlx genes to Hox clusters should help resolve this issue.

Ablation studies on the developing inner ear reveal a propensity for mirror duplications

“…7A,B). As a probe, we used the Xenopus homeobox gene Distalless 3 (X-dll3; actually Dlx5; Stock et al, 1996), which is strongly and globally expressed in the otic placode and otocyst (Papalopulu and Kintner, 1993). We have found that X-dll3 is expressed in prospective otic regions well before placode formation (stage 13, which is just after gastrulation), making it one of the earliest otic genes expressed in Xenopus, although not earlier than the transcription factors Sox9 and Pax8 (Saint-Germain et al, 2004).…”

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

“…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). However, not all epithelia adjacent to sites of bone formation (e.g., opercular bone, branchiostegal rays) exhibit dlx3b expression.…”

“…The zebrafish is known to possess eight dlx genes resulting from an additional genome duplication in the lineage leading to teleosts (Ekker et al, 1992;Akimenko et al, 1994;Stock et al, 1996;Ellies et al, 1997). Six of these dlx genes are found in three convergently transcribed pairs (dlx1a-dlx2a, dlx3b-dlx4b, dlx5a-dlx6a), as in their mammalian orthologs (the nomenclature used throughout this study follows that proposed by Panganiban and Rubenstein, 2002).…”

Jaw transformation with gain of symmetry after Dlx5/Dlx6 inactivation: Mirror of the past?

“…Based on sequencing comparison, it is thought that during the evolution of chordates an initial gene duplication occurred, followed by several cluster duplications and selective gene losses (Stock et al, 1996;Ruddle, 1997;Zerucha and Ekker, 2000). Dll homologs have been isolated from vertebrate species like lamprey, zebrafish, newt, Xenopus, mouse, and human (see Neidert et al, 2001, and references therein).…”