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dc.contributor.authorContreras, Esteban G
dc.contributor.authorEgger, Boris
dc.contributor.authorGold, Katrina S
dc.contributor.authorBrand, Andrea
dc.date.accessioned2018-12-18T00:33:16Z
dc.date.available2018-12-18T00:33:16Z
dc.date.issued2018-11-22
dc.identifier.issn1749-8104
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287126
dc.description.abstractBACKGROUND: Neural stem cells generate all of the neurons and glial cells in the central nervous system, both during development and in the adult to maintain homeostasis. In the Drosophila optic lobe, neuroepithelial cells progress through two transient progenitor states, PI and PII, before transforming into neuroblasts. Here we analyse the role of Notch signalling in the transition from neuroepithelial cells to neuroblasts. RESULTS: We observed dynamic regulation of Notch signalling: strong activity in PI progenitors, low signalling in PII progenitors, and increased activity after neuroblast transformation. Ectopic expression of the Notch ligand Delta induced the formation of ectopic PI progenitors. Interestingly, we show that the E3 ubiquitin ligase, Neuralized, regulates Delta levels and Notch signalling activity at the transition zone. We demonstrate that the proneural transcription factor, Lethal of scute, is essential to induce expression of Neuralized and promote the transition from the PI progenitor to the PII progenitor state. CONCLUSIONS: Our results show dynamic regulation of Notch signalling activity in the transition from neuroepithelial cells to neuroblasts. We propose a model in which Lethal of scute activates Notch signalling in a non-cell autonomous manner by regulating the expression of Neuralized, thereby promoting the progression between different neural stem cell states.
dc.format.mediumElectronic
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNeurons
dc.subjectNeuroepithelial Cells
dc.subjectAnimals
dc.subjectAnimals, Genetically Modified
dc.subjectDrosophila
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectDrosophila Proteins
dc.subjectMembrane Proteins
dc.subjectSignal Transduction
dc.subjectGene Expression Regulation, Developmental
dc.subjectReceptors, Notch
dc.subjectOptic Lobe, Nonmammalian
dc.subjectNeurogenesis
dc.subjectNeural Stem Cells
dc.titleDynamic Notch signalling regulates neural stem cell state progression in the Drosophila optic lobe.
dc.typeArticle
prism.issueIdentifier1
prism.publicationDate2018
prism.publicationNameNeural Dev
prism.startingPage25
prism.volume13
dc.identifier.doi10.17863/CAM.34435
dcterms.dateAccepted2018-11-13
rioxxterms.versionofrecord10.1186/s13064-018-0123-8
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-11-22
dc.contributor.orcidBrand, Andrea [0000-0002-2089-6954]
dc.identifier.eissn1749-8104
rioxxterms.typeJournal Article/Review
pubs.funder-project-idWellcome Trust (092545/Z/10/Z)
pubs.funder-project-idWellcome Trust (103792/Z/14/Z)
pubs.funder-project-idRoyal Society (RP150061)
pubs.funder-project-idWellcome Trust (092096/Z/10/Z)
pubs.funder-project-idCancer Research Uk (None)
cam.issuedOnline2018-11-22


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International