par Van Campenhout, Claude ;Thelie, Aurore ;Desiderio, Simon ;Hanotel, Julie ;Kricha, Sadia ;Bellefroid, Eric
Référence Gordon-Kenan Research Seminar(Neural Development (GRS) Gordon-Kenan Research Seminar From Stem Cells to Circuits August 9-10, 2014 Salve Regina University), Gordon-Kenan Research Seminar
Publication Publié, 2014
Abstract de conférence
Résumé : Prdm zinc finger transcription factors act as epigenetic regulators of gene expression in many developmental processes and their deregulation has been associated with human diseases. Here we show that Prdm12 is expressed in specific regions of the fore- and midbrain, cranial placodes, and in p1 spinal cord progenitors in the Xenopus embryo and that this restricted expression profile is conserved in the zebrafish, chick and mouse embryos, Prdm12 being in addition strongly expressed in those species in dorsal root ganglia. We found that Prdm12 is dependent on Pax6 and that it is restricted to p1 progenitors due to the repressive action of the homeobox transcription factors Dbx1 and Nkx6.1. Knockdown experiments in the frog revealed that Prdm12 is required for eng1 expressing V1 interneurons. Conversely in Prdm12 overexpressing embryos, V1 interneurons are expanded while Dbx1 and Nkx6.1, expressed rescpectively in the adjacent p0 and p2 domains and promoting respectively V0 and V2 interneurons, are reduced. This ability of Prdm12 to induce eng1 is blocked by coinjection of Dbx1 or Nkx6.1. Overexpression of Prdm12 in the chick neural tube leads as well to a dramatic increase of eng1 and of other markers representative of the different V1 interneuron subpopulations. Finally, we show that an Engrailed-Prdm12, but not VP16-Prdm12, has a V1 inducing activity similar to that of native Prdm12, and that Prdm12 activity requires both its PR and zinc finger domains. Together, our results indicate that Prdm12 acts in ventral spinal cord progenitors a general determinant of V1 cell fate by functioning as a transcriptional repressor and through cross-regulatory interactions with Dbx1 and Nkx6.1.