title: microRNA-34a regulates neurite outgrowth, spinal morphology, and function.
abstract: The p53 family member TAp73 is a transcription factor that plays a key role in many biological processes, including neuronal development. In particular, we have shown that p73 drives the expression of miR-34a, but not miR-34b and c, in mouse cortical neurons. miR-34a in turn modulates the expression of synaptic targets including synaptotagmin-1 and syntaxin-1A. Here we show that this axis is retained in mouse ES cells committed to differentiate toward a neurological phenotype. Moreover, overexpression of miR-34a alters hippocampal spinal morphology, and results in electrophysiological changes consistent with a reduction in spinal function. Therefore, the TAp73/miR-34a axis has functional relevance in primary neurons. These data reinforce a role for miR-34a in neuronal development.
authors.affiliation: Medical Research Council, Toxicology Unit,  Leicester University, Leicester LE1 9HN,  United Kingdom.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Agostini
authors.forename: Paola
authors.initials: P
authors.lastname: Tucci
authors.forename: Joern R
authors.initials: JR
authors.lastname: Steinert
authors.forename: Ruby
authors.initials: R
authors.lastname: Shalom-Feuerstein
authors.forename: Matthieu
authors.initials: M
authors.lastname: Rouleau
authors.forename: Daniel
authors.initials: D
authors.lastname: Aberdam
authors.forename: Ian D
authors.initials: ID
authors.lastname: Forsythe
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Young
authors.forename: Andrea
authors.initials: A
authors.lastname: Ventura
authors.forename: Carla P
authors.initials: CP
authors.lastname: Concepcion
authors.forename: Yoon-Chi
authors.initials: YC
authors.lastname: Han
authors.forename: Eleonora
authors.initials: E
authors.lastname: Candi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Knight
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D004594:Electrophysiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013131:Spine / Q000166:cytology* / Q000502:physiology; D050863:Synaptotagmin I / Q000378:metabolism; D050827:Syntaxin 1 / Q000378:metabolism
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D009687:Nuclear Proteins; D050863:Synaptotagmin I; D050827:Syntaxin 1; C494311:Syt1 protein, mouse; C454920:delta Np73, mouse