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Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus

Item Type:Article
Title:Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus
Creators Name:Thélie, A. and Desiderio, S. and Hanotel, J. and Quigley, I. and Van Driessche, B. and Rodari, A. and Borromeo, M.D. and Kricha, S. and Lahaye, F. and Croce, J. and Cerda-Moya, G. and Ordoño Fernandez, J. and Bolle, B. and Lewis, K.E. and Sander, M. and Pierani, A. and Schubert, M. and Johnson, J.E. and Kintner, C.R. and Pieler, T. and Van Lint, C. and Henningfeld, K.A. and Bellefroid, E.J. and Van Campenhout, C.
Abstract:V1 interneurons are inhibitory neurons that play an essential role in vertebrate locomotion. The molecular mechanisms underlying their genesis remain, however, largely undefined. Here, we show that the transcription factor Prdm12 is selectively expressed in p1 progenitors of the hindbrain and spinal cord in the frog embryo, and that a similar restricted expression profile is observed in the nerve cord of other vertebrates as well as of the cephalochordate amphioxus. Using frog, chick and mice, we analyzed the regulation of Prdm12 and found that its expression in the caudal neural tube is dependent on retinoic acid and Pax6, and that it is restricted to p1 progenitors, due to the repressive action of Dbx1 and Nkx6-1/2 expressed in the adjacent p0 and p2 domains. Functional studies in the frog, including genome-wide identification of its targets by RNA-seq and ChIP-Seq, reveal that vertebrate Prdm12 proteins act as a general determinant of V1 cell fate, at least in part, by directly repressing Dbx1 and Nkx6 genes. This probably occurs by recruiting the methyltransferase G9a, an activity that is not displayed by the amphioxus Prdm12 protein. Together, these findings indicate that Prdm12 promotes V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes, and suggest that this function might have only been acquired after the split of the vertebrate and cephalochordate lineages.
Keywords:Prdm, Interneuron, Neurogenesis, Spinal Cord, Transcription Factor, Animals, Mice, Xenopus tropicalis
Publisher:Company of Biologists
Page Range:3416-28
Date:1 October 2015
Official Publication:https://doi.org/10.1242/dev.121871
PubMed:View item in PubMed

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