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Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos
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 preci...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883443/ https://www.ncbi.nlm.nih.gov/pubmed/35225419 http://dx.doi.org/10.15252/msb.202110255 |
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author | Velten, Jessica Gao, Xuefan Van Nierop y Sanchez, Patrick Domsch, Katrin Agarwal, Rashi Bognar, Lena Paulsen, Malte Velten, Lars Lohmann, Ingrid |
author_facet | Velten, Jessica Gao, Xuefan Van Nierop y Sanchez, Patrick Domsch, Katrin Agarwal, Rashi Bognar, Lena Paulsen, Malte Velten, Lars Lohmann, Ingrid |
author_sort | Velten, Jessica |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8883443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88834432022-03-04 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 Mol Syst Biol Articles 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. John Wiley and Sons Inc. 2022-02-28 /pmc/articles/PMC8883443/ /pubmed/35225419 http://dx.doi.org/10.15252/msb.202110255 Text en ©2022 The Authors. Published under the terms of the CC BY 4.0 license https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles 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 |
title | Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos |
title_full | Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos |
title_fullStr | Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos |
title_full_unstemmed | Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos |
title_short | Single‐cell RNA sequencing of motoneurons identifies regulators of synaptic wiring in Drosophila embryos |
title_sort | single‐cell rna sequencing of motoneurons identifies regulators of synaptic wiring in drosophila embryos |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8883443/ https://www.ncbi.nlm.nih.gov/pubmed/35225419 http://dx.doi.org/10.15252/msb.202110255 |
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