The Xenopus doublesex-related gene Dmrt5 is required for olfactory placode neurogenesis.
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.
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.
Damien
D
Parlier
Virginie
V
Moers
Claude
C
Van Campenhout
Julie
J
Preillon
Lucas
L
Leclère
Amandine
A
Saulnier
Maria
M
Sirakov
Henriette
H
Busengdal
Sadia
S
Kricha
Jean-Christophe
JC
Marine
Fabian
F
Rentzsch
Eric J
EJ
Bellefroid
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D055785:Gene Knockdown Techniques; D020287:In Situ Nick-End Labeling; D055495:Neurogenesis / Q000502:physiology*; D009831:Olfactory Mucosa / Q000196:embryology*; D051857:Otx Transcription Factors / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012615:Sea Anemones / Q000235:genetics; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
C577680:DMRTA2 protein, Xenopus; D017931:DNA Primers; D018076:DNA, Complementary; D051857:Otx Transcription Factors; C497661:Otx2 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins