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dc.contributor.authorRaghu, SVen
dc.contributor.authorMohammad, Fen
dc.contributor.authorChua, JYen
dc.contributor.authorLam, JSWen
dc.contributor.authorLoberas, Men
dc.contributor.authorSahani, Sen
dc.contributor.authorBarros, CSen
dc.contributor.authorClaridge-Chang, Aen
dc.date.accessioned2018-09-03T23:03:50Z
dc.date.issued2018-08-20en
dc.identifier.issn1756-6606en
dc.identifier.urihttp://hdl.handle.net/10026.1/12222
dc.description.abstract

The analysis of behavior requires that the underlying neuronal circuits are identified and genetically isolated. In several major model species-most notably Drosophila-neurogeneticists identify and isolate neural circuits with a binary heterologous expression-control system: Gal4-UASG. One limitation of Gal4-UASG is that expression patterns are often too broad to map circuits precisely. To help refine the range of Gal4 lines, we developed an intersectional genetic AND operator. Interoperable with Gal4, the new system's key component is a fusion protein in which the DNA-binding domain of Gal4 has been replaced with a zinc finger domain with a different DNA-binding specificity. In combination with its cognate binding site (UASZ) the zinc-finger-replaced Gal4 ('Zal1') was functional as a standalone transcription factor. Zal1 transgenes also refined Gal4 expression ranges when combined with UASGZ, a hybrid upstream activation sequence. In this way, combining Gal4 and Zal1 drivers captured restricted cell sets compared with single drivers and improved genetic fidelity. This intersectional genetic AND operation presumably derives from the action of a heterodimeric transcription factor: Gal4-Zal1. Configurations of Zal1-UASZ and Zal1-Gal4-UASGZ are versatile tools for defining, refining, and manipulating targeted neural expression patterns with precision.

en
dc.format.extent46 - 46en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.titleA zinc-finger fusion protein refines Gal4-defined neural circuits.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30126464en
plymouth.issue1en
plymouth.volume11en
plymouth.journalMolecular Brainen
dc.identifier.doi10.1186/s13041-018-0390-7en
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/00 Groups by role
plymouth.organisational-group/Plymouth/00 Groups by role/Academics
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Biomedical Research Group/RC Reporting Group BRG
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Collaboration for the Advancement of Medical Education Research Assessment
plymouth.organisational-group/Plymouth/Faculty of Medicine and Dentistry/Neuroscience
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
dcterms.dateAccepted2018-08-06en
dc.rights.embargodate2018-09-05en
dc.identifier.eissn1756-6606en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1186/s13041-018-0390-7en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-08-20en
rioxxterms.typeJournal Article/Reviewen


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