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

Aurore Thélie, Simon Desiderio, Julie Hanotel, Ian Quigley, Benoit Van Driessche, Anthony Rodari, Mark D. Borromeo, Sadia Kricha, François Lahaye, Jenifer Croce, Gustavo Cerda-Moya, Jesús Ordoño Fernandez, Barbara Bolle, Katharine E. Lewis, Maike Sander, Alessandra Pierani, Michael Schubert, Jane E. Johnson, Christopher R. Kintner, Tomas Pieler & 4 others Carine Van Lint, Kristine A. Henningfeld, Eric J. Bellefroid, Claude Van Campenhout

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 genomewide 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.

Original languageEnglish (US)
Pages (from-to)3416-3428
Number of pages13
JournalDevelopment (Cambridge)
Volume142
Issue number19
DOIs
StatePublished - Oct 1 2015

Fingerprint

Interneurons
Xenopus
Vertebrates
Lancelets
Anura
Genes
Rhombencephalon
Neural Tube
Methyltransferases
Locomotion
Tretinoin
Spinal Cord
Proteins
Transcription Factors
Embryonic Structures
RNA
Neurons

Keywords

  • Interneuron
  • Neurogenesis
  • Prdm
  • Spinal cord
  • Transcription factor

ASJC Scopus subject areas

  • Developmental Biology
  • Molecular Biology

Cite this

Thélie, A., Desiderio, S., Hanotel, J., Quigley, I., Van Driessche, B., Rodari, A., ... Van Campenhout, C. (2015). Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. Development (Cambridge), 142(19), 3416-3428. https://doi.org/10.1242/dev.121871

Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. / Thélie, Aurore; Desiderio, Simon; Hanotel, Julie; Quigley, Ian; Van Driessche, Benoit; Rodari, Anthony; Borromeo, Mark D.; Kricha, Sadia; Lahaye, François; Croce, Jenifer; Cerda-Moya, Gustavo; Fernandez, Jesús Ordoño; Bolle, Barbara; Lewis, Katharine E.; Sander, Maike; Pierani, Alessandra; Schubert, Michael; Johnson, Jane E.; Kintner, Christopher R.; Pieler, Tomas; Van Lint, Carine; Henningfeld, Kristine A.; Bellefroid, Eric J.; Van Campenhout, Claude.

In: Development (Cambridge), Vol. 142, No. 19, 01.10.2015, p. 3416-3428.

Research output: Contribution to journalArticle

Thélie, A, Desiderio, S, Hanotel, J, Quigley, I, Van Driessche, B, Rodari, A, Borromeo, MD, Kricha, S, Lahaye, F, Croce, J, Cerda-Moya, G, Fernandez, JO, Bolle, B, Lewis, KE, Sander, M, Pierani, A, Schubert, M, Johnson, JE, Kintner, CR, Pieler, T, Van Lint, C, Henningfeld, KA, Bellefroid, EJ & Van Campenhout, C 2015, 'Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus', Development (Cambridge), vol. 142, no. 19, pp. 3416-3428. https://doi.org/10.1242/dev.121871
Thélie A, Desiderio S, Hanotel J, Quigley I, Van Driessche B, Rodari A et al. Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. Development (Cambridge). 2015 Oct 1;142(19):3416-3428. https://doi.org/10.1242/dev.121871
Thélie, Aurore ; Desiderio, Simon ; Hanotel, Julie ; Quigley, Ian ; Van Driessche, Benoit ; Rodari, Anthony ; Borromeo, Mark D. ; Kricha, Sadia ; Lahaye, François ; Croce, Jenifer ; Cerda-Moya, Gustavo ; Fernandez, Jesús Ordoño ; Bolle, Barbara ; Lewis, Katharine E. ; Sander, Maike ; Pierani, Alessandra ; Schubert, Michael ; Johnson, Jane E. ; Kintner, Christopher R. ; Pieler, Tomas ; Van Lint, Carine ; Henningfeld, Kristine A. ; Bellefroid, Eric J. ; Van Campenhout, Claude. / Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus. In: Development (Cambridge). 2015 ; Vol. 142, No. 19. pp. 3416-3428.
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AU - Cerda-Moya, Gustavo

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AU - Schubert, Michael

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