Single-cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos

Velten, Jessica; Gao, Xuefan; van Nierop y Sanchez, Patrick; Domsch, Katrin; Agarwal, Rashi; Bognar, Lena; Paulsen, Malte; Velten, Lars; Lohmann, Ingrid

Single-cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos

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dc.contributor.author Velten, Jessica
dc.contributor.author Gao, Xuefan
dc.contributor.author van Nierop y Sanchez, Patrick
dc.contributor.author Domsch, Katrin
dc.contributor.author Agarwal, Rashi
dc.contributor.author Bognar, Lena
dc.contributor.author Paulsen, Malte
dc.contributor.author Velten, Lars
dc.contributor.author Lohmann, Ingrid
dc.date.accessioned 2022-04-07T06:10:25Z
dc.date.available 2022-04-07T06:10:25Z
dc.date.issued 2022
dc.description.abstract The correct wiring of neuronal circuits is one of the most complex processes in development, since axons form highly specific connections out of a vast number of possibilities. Circuit structure is genetically determined in vertebrates and invertebrates, but the mechanisms guiding each axon to precisely innervate a unique pre-specified target cell are poorly understood. We investigated Drosophila embryonic motoneurons using single-cell genomics, imaging, and genetics. We show that a cell-specific combination of homeodomain transcription factors and downstream immunoglobulin domain proteins is expressed in individual cells and plays an important role in determining cell-specific connections between differentiated motoneurons and target muscles. We provide genetic evidence for a functional role of five homeodomain transcription factors and four immunoglobulins in the neuromuscular wiring. Knockdown and ectopic expression of these homeodomain transcription factors induces cell-specific synaptic wiring defects that are partly phenocopied by genetic modulations of their immunoglobulin targets. Taken together, our data suggest that homeodomain transcription factor and immunoglobulin molecule expression could be directly linked and function as a crucial determinant of neuronal circuit structure.
dc.description.sponsorship The project was funded by the DFG grant LO 844/4-2 to Ingrid Lohmann. Lars Velten acknowledges grant PID2019-108082GA-I00 by the Spanish Ministry of Science, Innovation and Universities (MCIU/AEI/FEDER, UE) as well as support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme / Generalitat de Catalunya. Open Access funding enabled and organized by ProjektDEAL
dc.format.mimetype application/pdf
dc.identifier.citation Velten J, Gao X, Van Nierop y Sanchez P, Domsch K, Agarwal R, Bognar L. Single-cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos. Mol Syst Biol. 2022 Mar;18(3):e10255. DOI: 10.15252/msb.202110255
dc.identifier.doi http://dx.doi.org/10.15252/msb.202110255
dc.identifier.issn 1744-4292
dc.identifier.uri http://hdl.handle.net/10230/52840
dc.language.iso eng
dc.publisher Wiley Open Access
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Drosòfila
dc.subject.other Embriologia
dc.subject.other Genètica
dc.title Single-cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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