title: Stabilization of Dll1 mRNA by Elavl1/HuR in neuroepithelial cells undergoing mitosis.
abstract: In the vertebrate neuroepithelium, the decision to differentiate is made by neural precursors soon after mitosis, when they are apically located. This process is controlled by lateral inhibitory signals triggered by the Delta/Notch pathway. During mitosis, the capacity of neural precursors to express the neurogenic genes Dll1 and Notch1 is maximal due to mRNA stabilization, but the mechanism controlling this process remains unknown. Here we show that Elav-like (Elavl1)/HuR becomes enriched in the cytoplasm of neuroepithelial cells undergoing mitosis and that this ribonucleoprotein interacts with the 3' untranslated region (UTR) of Dll1 mRNA. This interaction is functionally relevant because RNAi against Elavl1 reduces the stability of Dll1-3'UTR-containing transcripts in mitosis-arrested neuroepithelial cells, and Elavl1 null-mutant heterozygous mice show decreased Dll1 expression in the developing brain in vivo. We also show that RNAi against Elavl1 diminishes the capacity of brain precursors to trigger lateral inhibitory signals to their neighbors, an observation consistent with the increase in the rate of neurogenesis which can be detected in vivo in the developing retina of Elavl1 heterozygous mice. We conclude that Elavl1/HuR facilitates the exposure of vertebrate neuronal precursors to apically located Delta/Notch signals.
authors.affiliation: Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, IC-CSIC, 28002 Madrid, Spain.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: García-Domínguez
authors.forename: Dominique
authors.initials: D
authors.lastname: Morello
authors.forename: Elsa
authors.initials: E
authors.lastname: Cisneros
authors.forename: Dimitris L
authors.initials: DL
authors.lastname: Kontoyiannis
authors.forename: José M
authors.initials: JM
authors.lastname: Frade
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D002642:Chick Embryo; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D018274:Electroporation; D005260:Female; D005786:Gene Expression Regulation; D020868:Gene Silencing; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008938:Mitosis / Q000502:physiology; D046569:Neuroepithelial Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D000954:Antigens, Surface; D002135:Calcium-Binding Proteins; C519665:DLL4 protein, mouse; C512925:Dlk1 protein, mouse; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051881:Receptor, Notch1