Laboratoire de Génétique du Développement, Université Libre de Bruxelles, Institut de Biologie et de Médecine Moléculaires (IBMM), rue des Profs. Jeener et Brachet 12, B-6041 Gosselies, Belgium.
Dev Biol. 2013 Jan 1;373(1):39-52. doi: 10.1016/j.ydbio.2012.10.003. Epub 2012 Oct 9.
The Dmrt (doublesex and mab-3 related transcription factor) genes encode a large family of evolutionarily conserved transcription factors whose function in sex specific differentiation has been well studied in all animal lineages. In vertebrates, their function is not restricted to the developing gonads. For example, Xenopus Dmrt4 is essential for neurogenesis in the olfactory system. Here we have isolated and characterized Xenopus Dmrt5 and found that it is coexpressed with Dmrt4 in the developing olfactory placodes. As Dmrt4, Dmrt5 is positively regulated in the ectoderm by neural inducers and negatively by proneural factors. Both Dmrt5 and Dmrt4 genes are also activated by the combined action of the transcription factor Otx2, broadly transcribed in the head ectoderm and of Notch signaling, activated in the anterior neural ridge. As for Dmrt4, knockdown of Dmrt5 impairs neurogenesis in the embryonic olfactory system and in neuralized animal caps. Conversely, its overexpression promotes neuronal differentiation in animal caps, a property that requires the conserved C-terminal DMA and DMB domains. We also found that the sea anenome Dmrt4/5 related gene NvDmrtb also induces neurogenesis in Xenopus animal caps and that conversely, its knockdown in Nematostella reduces elav-1 positive neurons. Together, our data identify Dmrt5 as a novel important regulator of neurogenesis whose function overlaps with that of Dmrt4 during Xenopus olfactory system development. They also suggest that Dmrt may have had a role in neurogenesis in the last common ancestor of cnidarians and bilaterians.
Dmrt（双倍性别和 mab-3 相关转录因子）基因编码一个进化上保守的转录因子大家族，其在性别特异性分化中的功能已在所有动物谱系中得到很好的研究。在脊椎动物中，它们的功能不仅限于发育中的性腺。例如，非洲爪蟾 Dmrt4 对嗅觉系统的神经发生是必不可少的。在这里，我们分离并鉴定了非洲爪蟾 Dmrt5，并发现它与 Dmrt4 在发育中的嗅基板中共同表达。与 Dmrt4 一样，Dmrt5 在表皮中受神经诱导物的正调控，受神经前体细胞因子的负调控。Dmrt5 和 Dmrt4 基因都被转录因子 Otx2 广泛转录于头部表皮层和 Notch 信号激活的前神经嵴联合激活。与 Dmrt4 一样，Dmrt5 的敲低会损害胚胎嗅觉系统和神经化动物帽中的神经发生。相反，其过表达促进动物帽中的神经元分化，这一特性需要保守的 C 端 DMA 和 DMB 结构域。我们还发现海葵 Dmrt4/5 相关基因 NvDmrtb 也能诱导非洲爪蟾动物帽中的神经发生，反之，其在海葵 Nematostella 中的敲低会减少 elav-1 阳性神经元。总之，我们的数据确定 Dmrt5 是神经发生的一个新的重要调节因子，其功能与非洲爪蟾嗅觉系统发育过程中的 Dmrt4 重叠。它们还表明，Dmrt 可能在刺胞动物和两侧对称动物的最后共同祖先的神经发生中发挥了作用。
