The doublesex-related gene, XDmrt4, is required for neurogenesis in the olfactory system

The Dmrt genes encode a large family of transcription factors whose function in sexual development has been well studied. However, their expression pattern is not restricted to the gonad, suggesting that Dmrt genes might regulate other developmental processes. Here, we report the expression and functional analysis of one member of this family: Xenopus Dmrt4 (XDmrt4). XDmrt4 is initially expressed in the anterior neural ridge and then becomes progressively restricted to part of the telencephalon and the olfactory placode/epithelium. XDmrt4 is induced at the anterior neural plate by a balance of neural inducers and caudalizing factors. Interference with XDmrt4 function by injection of a morpholino oligonucleotide or an inhibitory mutant resulted in a similar phenotype, the specific disruption of the olfactory placode expression of Xebf2 without affecting the expression of other placodal markers. Xebf2 belongs to a family of helix-loop-helix transcription factors implicated in neuronal differentiation, and later in embryogenesis XDmrt4-deficient embryos show impaired neurogenesis in the olfactory epithelium. Consistent with this finding, XDmrt4 is sufficient to activate neurogenin, Xebf2, and neural cell adhesion molecule expression in animal explants and is required for Noggin-mediated neuralization. Altogether, these results indicate that XDmrt4 is an important regulator of neurogenesis in the olfactory system upstream of neurogenin and Xebf2.