title: The positive transcriptional elongation factor (P-TEFb) is required for neural crest specification.
abstract: Regulation of gene expression at the level of transcriptional elongation has been shown to be important in stem cells and tumour cells, but its role in the whole animal is only now being fully explored. Neural crest cells (NCCs) are a multipotent population of cells that migrate during early development from the dorsal neural tube throughout the embryo where they differentiate into a variety of cell types including pigment cells, cranio-facial skeleton and sensory neurons. Specification of NCCs is both spatially and temporally regulated during embryonic development. Here we show that components of the transcriptional elongation regulatory machinery, CDK9 and CYCLINT1 of the P-TEFb complex, are required to regulate neural crest specification. In particular, we show that expression of the proto-oncogene c-Myc and c-Myc responsive genes are affected. Our data suggest that P-TEFb is crucial to drive expression of c-Myc, which acts as a 'gate-keeper' for the correct temporal and spatial development of the neural crest.
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Hatch
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Marta
authors.initials: M
authors.lastname: Marin-Barba
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Moxon
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Ford
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Nicole J
authors.initials: NJ
authors.lastname: Ward
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Tomlinson
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Ines
authors.initials: I
authors.lastname: Desanlis
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Adam E
authors.initials: AE
authors.lastname: Hendry
authors.affiliation: Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Saartje
authors.initials: S
authors.lastname: Hontelez
authors.affiliation: Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Ila
authors.initials: I
authors.lastname: van Kruijsbergen
authors.affiliation: Radboud University, Department of Molecular Developmental Biology, Faculty of Science, Radboud Institute for Molecular Life Sciences, Nijmegen, The Netherlands.
authors.forename: Gert Jan C
authors.initials: GJ
authors.lastname: Veenstra
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Münsterberg
authors.affiliation: School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, UK. Electronic address: grant.wheeler@uea.ac.uk.
authors.forename: Grant N
authors.initials: GN
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D056906:Cyclin T / Q000172:deficiency / Q000235:genetics*; D042863:Cyclin-Dependent Kinase 9 / Q000172:deficiency / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D016259:Genes, myc; D007555:Isoxazoles / Q000494:pharmacology; D000077339:Leflunomide; D060172:Morpholinos / Q000494:pharmacology; D009432:Neural Crest / Q000196:embryology*; D042925:Positive Transcriptional Elongation Factor B / Q000172:deficiency / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D012319:RNA Polymerase II / Q000378:metabolism; D055757:SOXE Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D061805:Transcription Elongation, Genetic / Q000187:drug effects; D014158:Transcription, Genetic; D029867:Xenopus Proteins / Q000172:deficiency / Q000235:genetics*; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics
chemical_list: D056906:Cyclin T; D007555:Isoxazoles; D060172:Morpholinos; D016271:Proto-Oncogene Proteins c-myc; D055757:SOXE Transcription Factors; D029867:Xenopus Proteins; D042925:Positive Transcriptional Elongation Factor B; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II; D000077339:Leflunomide
keywords: Cdk9; CyclinT1; Leflunomide; Neural crest cells; P-TEFb; Polymerase pausing; Transcriptional elongation; Xenopus; c-Myc