title: Prdm12 specifies V1 interneurons through cross-repressive interactions with Dbx1 and Nkx6 genes in Xenopus.
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.
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium.
authors.forename: Aurore
authors.initials: A
authors.lastname: Thélie
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium.
authors.forename: Simon
authors.initials: S
authors.lastname: Desiderio
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Hanotel
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Quigley
authors.affiliation: Laboratory of Molecular Virology, ULB, IBMM, Gosselies B-6041, Belgium.
authors.forename: Benoit
authors.initials: B
authors.lastname: Van Driessche
authors.affiliation: Laboratory of Molecular Virology, ULB, IBMM, Gosselies B-6041, Belgium.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodari
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Borromeo
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium.
authors.forename: Sadia
authors.initials: S
authors.lastname: Kricha
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, CNRS UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer (UMR 7009), Observatoire Océanologique de Villefranche-sur-Mer, Villefranche-sur-Mer 06230, France.
authors.forename: François
authors.initials: F
authors.lastname: Lahaye
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, CNRS UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer (UMR 7009), Observatoire Océanologique de Villefranche-sur-Mer, Villefranche-sur-Mer 06230, France.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Croce
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Cerda-Moya
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ordoño Fernandez
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bolle
authors.affiliation: Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA.
authors.forename: Katharine E
authors.initials: KE
authors.lastname: Lewis
authors.affiliation: Departments of Pediatrics and Cellular and Molecular Medicine, Pediatric Diabetes Research Center, University of California, San Diego, La Jolla, CA 92093-0695, USA.
authors.forename: Maike
authors.initials: M
authors.lastname: Sander
authors.affiliation: Génétique et développement du cortex cerebral, Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Sorbonne Paris Cité, Paris Cedex 13 75205, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pierani
authors.affiliation: Sorbonne Universités, UPMC Université Paris 06, CNRS UMR 7009, Laboratoire de Biologie du Développement de Villefranche-sur-Mer (UMR 7009), Observatoire Océanologique de Villefranche-sur-Mer, Villefranche-sur-Mer 06230, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Schubert
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Johnson
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Kintner
authors.affiliation: Department of Developmental Biochemistry, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Göttingen, 37077 Göttingen, Germany.
authors.forename: Tomas
authors.initials: T
authors.lastname: Pieler
authors.affiliation: Laboratory of Molecular Virology, ULB, IBMM, Gosselies B-6041, Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Van Lint
authors.affiliation: Department of Developmental Biochemistry, Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), University of Göttingen, 37077 Göttingen, Germany.
authors.forename: Kristine A
authors.initials: KA
authors.lastname: Henningfeld
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium ebellefr@ulb.ac.be cvcampen@ulb.ac.be.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Bellefroid
authors.affiliation: Laboratory of Developmental Genetics, Université Libre de Bruxelles (ULB), Institute of Molecular Biology and Medecine (IBMM) and ULB Neuroscience Institute, Gosselies B-6041, Belgium ebellefr@ulb.ac.be cvcampen@ulb.ac.be.
authors.forename: Claude
authors.initials: C
authors.lastname: Van Campenhout
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism*; D002642:Chick Embryo; D047369:Chromatin Immunoprecipitation; D019295:Computational Biology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008969:Molecular Sequence Data; D009024:Morphogenesis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D066293:Renshaw Cells / Q000502:physiology*; D012249:Rhombencephalon / Q000378:metabolism; D017423:Sequence Analysis, RNA; D013045:Species Specificity; D013116:Spinal Cord / Q000378:metabolism; D014981:Xenopus / Q000196:embryology*
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C000597359:PRDM12 protein, Xenopus laevis
keywords: Interneuron; Neurogenesis; Prdm; Spinal cord; Transcription factor