title: miR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition.
abstract: During neurogenesis, generation, migration and integration of the correct numbers of each neuron sub-type depends on complex molecular interactions in space and time. MicroRNAs represent a key control level allowing the flexibility and stability needed for this process. Insight into the role of this regulatory pathway in the brain is still limited. We performed a sequential experimental approach using postnatal olfactory bulb neurogenesis in mice, starting from global expression analyses to the investigation of functional interactions between defined microRNAs and their targets. Deep sequencing of small RNAs extracted from defined compartments of the postnatal neurogenic system demonstrated that the miR-200 family is specifically induced during late neuronal differentiation stages. Using in vivo strategies we interfered with the entire miR-200 family in loss- and gain-of-function settings, showing a role of miR-200 in neuronal maturation. This function is mediated by targeting the transcription factor Zeb2. Interestingly, so far functional interaction between miR-200 and Zeb2 has been exclusively reported in cancer or cultured stem cells. Our data demonstrate that this regulatory interaction is also active during normal neurogenesis.
authors: IBDM, Aix-Marseille Université, CNRS, UMR7288, 13288 Marseille, France.
authors: Christophe
authors: C
authors: Beclin
authors: IBDM, Aix-Marseille Université, CNRS, UMR7288, 13288 Marseille, France.
authors: Philipp
authors: P
authors: Follert
authors: Laboratory of Molecular Biology, Dept Development and Regeneration, KULeuven, 3000 Leuven, Belgium.
authors: Elke
authors: E
authors: Stappers
authors: IBDM, Aix-Marseille Université, CNRS, UMR7288, 13288 Marseille, France.|Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors: Serena
authors: S
authors: Barral
authors: IBDM, Aix-Marseille Université, CNRS, UMR7288, 13288 Marseille, France.
authors: Nathalie
authors: N
authors: Coré
authors: IBDM, Aix-Marseille Université, CNRS, UMR7288, 13288 Marseille, France.
authors: Antoine
authors: A
authors: de Chevigny
authors: CNRS and University Nice Sophia Antipolis, IPMC, Sophia Antipolis, France.
authors: Virginie
authors: V
authors: Magnone
authors: CNRS and University Nice Sophia Antipolis, IPMC, Sophia Antipolis, France.
authors: Kévin
authors: K
authors: Lebrigand
authors: Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors: Ute
authors: U
authors: Bissels
authors: Laboratory of Molecular Biology, Dept Development and Regeneration, KULeuven, 3000 Leuven, Belgium.|Dept Cell Biology, Erasmus MC, 3015 CN Rotterdam, The Netherlands.
authors: Danny
authors: D
authors: Huylebroeck
authors: Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors: Andreas
authors: A
authors: Bosio
authors: CNRS and University Nice Sophia Antipolis, IPMC, Sophia Antipolis, France.
authors: Pascal
authors: P
authors: Barbry
authors: Laboratory of Molecular Biology, Dept Development and Regeneration, KULeuven, 3000 Leuven, Belgium.|GIGA-Neurosciences, Université de Liège, 4000 Liège, Belgium.
authors: Eve
authors: E
authors: Seuntjens
authors: IBDM, Aix-Marseille Université, CNRS, UMR7288, 13288 Marseille, France.
authors: Harold
authors: H
authors: Cremer
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics* / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009830:Olfactory Bulb / Q000254:growth & development / Q000378:metabolism; D016548:Prosencephalon / Q000254:growth & development* / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D000074165:Zinc Finger E-box Binding Homeobox 2 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; C120602:ZEB2 protein, mouse; D000074165:Zinc Finger E-box Binding Homeobox 2