Insights into the Evolutionary History of the Vertebrate Zic3 Locus from a Teleost-specific Zic6 Gene in the Zebrafish, Danio Rerio

The Zic gene family of zinc-finger transcription factors includes five orthologues, zic1-5, that are common to the Euteleostian vertebrates (fish, frogs, birds, and mammals). The Zic genes have been implicated as regulators of a number of critical developmental processes, including neurulation, neuronal differentiation, neural crest specification, the establishment of left-right asymmetry, and regulation of cell proliferation. The different Zic genes encode proteins that are expressed in broadly overlapping spatial domains, have conserved DNA-binding domains that recognize a common motif, are capable of physical interactions, and can co-regulate one another's transcription. Thus, the transcriptional regulation of individual proteins and their effects on downstream targets must be assessed within the context of co-expression with other family members. We describe a novel gene, zic6, that is specific to the teleost fishes and lacks the lateral and rostral expression domains typical of the other Zic family members. We present evidence that zic6 is an ancestral locus arising by chromosomal duplication early in the Euteleostomi that was subsequently lost in the terrestrial vertebrates.