Three structurally and functionally conserved Hlx genes in zebrafish.

For the Hlx class, which includes homeodomains (HD) that are similar to Drosophila H2.0, few members have been identified in vertebrates. In this report, we describe three zebrafish genes, hlx1, hlx2 and hlx3, related to the murine Dbx genes. The proteins encoded by hlx1 and hlx2 have about the same sequence identity to Dbx1 (approximately 60%), suggesting that they derive from a duplication in the fish lineage. This is supported by similarities in the embryonic expression patterns and promoter sequence conservation. The zebrafish Hlx3 protein is related to murine Dbx2, but it is apparently too diverged to be orthologous. Our phylogenetic analysis of all the known HD sequences of the Hlx class also shows that it can be divided into at least two distinct families. All the Dbx-like genes have similar expression in the embryonic nervous system. However, the initial expression patterns of the zebrafish hlx genes are quite unique, suggesting that some functional divergence has occurred between fish and mammals.