title: miR-9 controls the timing of neurogenesis through the direct inhibition of antagonistic factors.
abstract: The timing of commitment and cell-cycle exit within progenitor populations during neurogenesis is a fundamental decision that impacts both the number and identity of neurons produced during development. We show here that microRNA-9 plays a key role in this process through the direct inhibition of targets with antagonistic functions. Across the ventricular zone of the developing zebrafish hindbrain, miR-9 expression occurs at a range of commitment stages. Abrogating miR-9 function transiently delays cell-cycle exit, leading to the increased generation of late-born neuronal populations. Target protection analyses in vivo identify the progenitor-promoting genes her6 and zic5 and the cell-cycle exit-promoting gene elavl3/HuC as sequential targets of miR-9 as neurogenesis proceeds. We propose that miR-9 activity generates an ambivalent progenitor state poised to respond to both progenitor maintenance and commitment cues, which may be necessary to adjust neuronal production to local extrinsic signals during late embryogenesis.
authors.affiliation: Zebrafish Neurogenetics Group, Laboratory of Neurobiology and Development, CNRS UPR 3294, Institute of Neurobiology Alfred Fessard, 91198 Gif-sur-Yvette Cédex, France. coolen@inaf.cnrs-gif.fr
authors.forename: Marion
authors.initials: M
authors.lastname: Coolen
authors.forename: Denis
authors.initials: D
authors.lastname: Thieffry
authors.forename: Øyvind
authors.initials: Ø
authors.lastname: Drivenes
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Becker
authors.forename: Laure
authors.initials: L
authors.lastname: Bally-Cuif
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism; D000067778:ELAV-Like Protein 3; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D015027:Zebrafish / Q000235:genetics / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D000409:Alanine; D001381:Azepines; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D051959:ELAV Proteins; D000067778:ELAV-Like Protein 3; D035683:MicroRNAs; D029961:Zebrafish Proteins; C426854:Her6 protein, zebrafish; C573942:MIRN9 microRNA, zebrafish; C484278:N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide; C493010:Zic5 protein, zebrafish; C088635:elavl3 protein, zebrafish