title: A self-organizing miR-132/Ctbp2 circuit regulates bimodal notch signals and glial progenitor fate choice during spinal cord maturation.
abstract: Radial glial progenitors play pivotal roles in the development and patterning of the spinal cord, and their fate is controlled by Notch signaling. How Notch is shaped to regulate their crucial transition from expansion toward differentiation remains, however, unknown. miR-132 in the developing zebrafish dampens Notch signaling via a cascade involving the transcriptional corepressor Ctbp2 and the Notch suppressor Sirt1. At early embryonic stages, high Ctbp2 levels sustain Notch signaling and radial glial expansion and concomitantly induce miR-132 expression via a double-negative feedback loop involving Rest inhibition. The changing balance in miR-132 and Ctbp2 interaction gradually drives the switch in Notch output and radial glial progenitor fate as part of the larger developmental program involved in the transition from embryonic to larval spinal cord.
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; Center for Human Genetics and Leuven Institute for Neurodegenerative Disorders, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Evgenia
authors.initials: E
authors.lastname: Salta
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; Center for Human Genetics and Leuven Institute for Neurodegenerative Disorders, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Lau
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; Center for Human Genetics and Leuven Institute for Neurodegenerative Disorders, KU Leuven, 3000 Leuven, Belgium.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala Frigerio
authors.affiliation: Zebrafish Neurogenetics Group, Laboratory of Neurobiology and Development, CNRS UPR 3294, Institute of Neurobiology Alfred Fessard, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cédex, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Coolen
authors.affiliation: Zebrafish Neurogenetics Group, Laboratory of Neurobiology and Development, CNRS UPR 3294, Institute of Neurobiology Alfred Fessard, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cédex, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Bally-Cuif
authors.affiliation: VIB Center for the Biology of Disease, 3000 Leuven, Belgium; Center for Human Genetics and Leuven Institute for Neurodegenerative Disorders, KU Leuven, 3000 Leuven, Belgium; Institute of Neurology, University College London, Queen Square, WC1N 3BG London, UK. Electronic address: bart.destrooper@cme.vib-kuleuven.be.
authors.forename: Bart
authors.initials: B
authors.lastname: De Strooper
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005136:Eye Proteins; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
chemical_list: D005136:Eye Proteins; D035683:MicroRNAs; D051880:Receptors, Notch; D012097:Repressor Proteins; D056564:Sirtuin 1; D029961:Zebrafish Proteins; D000099229:RE1-Silencing Transcription Factor; C577847:ctbp2a protein, zebrafish; C000592936:mirn132 microRNA, zebrafish