A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord

Understanding developmental changes in neuronal lineages is crucial to elucidate how they assemble into functional neural networks. Studies investigating nervous system development in model systems have only focused on select regions of the CNS due to the limited availability of genetic drivers that...

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Main Authors: Jelly HM Soffers, Erin Beck, Daniel J Sytkowski, Marianne E Maughan, Devasri Devarakonda, Yi Zhu, Beth A Wilson, Yu-Chieh David Chen, Ted Erclik, James W Truman, James B Skeath, Haluk Lacin
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Language:English
Published: eLife Sciences Publications Ltd 2025-06-01
Series:eLife
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Online Access:https://elifesciences.org/articles/106042
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author Jelly HM Soffers
Erin Beck
Daniel J Sytkowski
Marianne E Maughan
Devasri Devarakonda
Yi Zhu
Beth A Wilson
Yu-Chieh David Chen
Ted Erclik
James W Truman
James B Skeath
Haluk Lacin
author_facet Jelly HM Soffers
Erin Beck
Daniel J Sytkowski
Marianne E Maughan
Devasri Devarakonda
Yi Zhu
Beth A Wilson
Yu-Chieh David Chen
Ted Erclik
James W Truman
James B Skeath
Haluk Lacin
author_sort Jelly HM Soffers
collection DOAJ
description Understanding developmental changes in neuronal lineages is crucial to elucidate how they assemble into functional neural networks. Studies investigating nervous system development in model systems have only focused on select regions of the CNS due to the limited availability of genetic drivers that target specific neuronal lineages throughout development and adult life. This has hindered our understanding of how distinct neuronal lineages interconnect to form neuronal circuits during development. Here, we present a split-GAL4 library composed of genetic driver lines, which we generated via editing the genomic locus of lineage-specific transcription factors and demonstrate that we can use this library to specifically target most individual neuronal hemilineages in the Drosophila ventral nerve cord (VNC) throughout development and into adulthood. Using these genetic driver lines, we found striking morphological changes in neuronal processes within a lineage during metamorphosis. We also demonstrated how neurochemical features of neuronal classes can be quickly assessed. Lastly, we documented behaviors elicited in response to optogenetic activation of individual neuronal lineages and generated a comprehensive lineage-behavior map of the entire fly VNC. Looking forward, this lineage-specific split-GAL4 driver library will provide the genetic tools needed to address the questions emerging from the analysis of the recent VNC connectome and transcriptome datasets.
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spelling doaj-art-d15ffd63cd2f4d218eb76229211aba8e2025-08-20T03:11:03ZengeLife Sciences Publications LtdeLife2050-084X2025-06-011410.7554/eLife.106042A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cordJelly HM Soffers0https://orcid.org/0000-0002-1051-7375Erin Beck1Daniel J Sytkowski2Marianne E Maughan3Devasri Devarakonda4Yi Zhu5Beth A Wilson6Yu-Chieh David Chen7https://orcid.org/0000-0002-2597-7577Ted Erclik8James W Truman9https://orcid.org/0000-0002-9209-5435James B Skeath10https://orcid.org/0000-0003-1179-4857Haluk Lacin11https://orcid.org/0000-0003-2468-9618School of Science and Engineering, Division Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, United StatesSchool of Science and Engineering, Division Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, United StatesSchool of Science and Engineering, Division Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, United StatesSchool of Science and Engineering, Division Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, United StatesSchool of Science and Engineering, Division Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, United StatesDepartment of Genetics, Washington University School of Medicine, St. Louis, United StatesDepartment of Genetics, Washington University School of Medicine, St. Louis, United StatesDepartment of Biology, New York University, New York, United StatesDepartment of Biology, University of Toronto - Mississauga, Mississauga, Canada; Department of Cell and Systems Biology, University of Toronto - Mississauga, Mississauga, CanadaDepartment of Biology, University of Washington, Seattle, United StatesDepartment of Genetics, Washington University School of Medicine, St. Louis, United StatesSchool of Science and Engineering, Division Biological and Biomedical Systems, University of Missouri-Kansas City, Kansas City, United StatesUnderstanding developmental changes in neuronal lineages is crucial to elucidate how they assemble into functional neural networks. Studies investigating nervous system development in model systems have only focused on select regions of the CNS due to the limited availability of genetic drivers that target specific neuronal lineages throughout development and adult life. This has hindered our understanding of how distinct neuronal lineages interconnect to form neuronal circuits during development. Here, we present a split-GAL4 library composed of genetic driver lines, which we generated via editing the genomic locus of lineage-specific transcription factors and demonstrate that we can use this library to specifically target most individual neuronal hemilineages in the Drosophila ventral nerve cord (VNC) throughout development and into adulthood. Using these genetic driver lines, we found striking morphological changes in neuronal processes within a lineage during metamorphosis. We also demonstrated how neurochemical features of neuronal classes can be quickly assessed. Lastly, we documented behaviors elicited in response to optogenetic activation of individual neuronal lineages and generated a comprehensive lineage-behavior map of the entire fly VNC. Looking forward, this lineage-specific split-GAL4 driver library will provide the genetic tools needed to address the questions emerging from the analysis of the recent VNC connectome and transcriptome datasets.https://elifesciences.org/articles/106042VNCneuronal lineagesGAL4 librarybehaviorneurodevelopmentscRNA seq
spellingShingle Jelly HM Soffers
Erin Beck
Daniel J Sytkowski
Marianne E Maughan
Devasri Devarakonda
Yi Zhu
Beth A Wilson
Yu-Chieh David Chen
Ted Erclik
James W Truman
James B Skeath
Haluk Lacin
A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord
eLife
VNC
neuronal lineages
GAL4 library
behavior
neurodevelopment
scRNA seq
title A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord
title_full A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord
title_fullStr A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord
title_full_unstemmed A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord
title_short A library of lineage-specific driver lines connects developing neuronal circuits to behavior in the Drosophila ventral nerve cord
title_sort library of lineage specific driver lines connects developing neuronal circuits to behavior in the drosophila ventral nerve cord
topic VNC
neuronal lineages
GAL4 library
behavior
neurodevelopment
scRNA seq
url https://elifesciences.org/articles/106042
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