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The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function

Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron–glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of...

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Detalles Bibliográficos
Autores principales: Coutinho-Budd, Jaeda C., Sheehan, Amy E., Freeman, Marc R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733495/
https://www.ncbi.nlm.nih.gov/pubmed/29138279
http://dx.doi.org/10.1101/gad.305888.117
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author Coutinho-Budd, Jaeda C.
Sheehan, Amy E.
Freeman, Marc R.
author_facet Coutinho-Budd, Jaeda C.
Sheehan, Amy E.
Freeman, Marc R.
author_sort Coutinho-Budd, Jaeda C.
collection PubMed
description Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron–glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of Drosophila cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia–soma interactions. We show that cortex glia tile with one another and with astrocytes to establish unique central nervous system (CNS) spatial domains that actively restrict glial growth, and selective ablation of cortex glia causes animal lethality. In an RNAi-based screen, we identified αSNAP (soluble NSF [N-ethylmalemeide-sensitive factor] attachment protein α) and several components of vesicle fusion and recycling machinery as essential for the maintenance of cortex glial morphology and continued contact with neurons. Interestingly, loss of the secreted neurotrophin Spätzle 3 (Spz3) phenocopied αSNAP phenotypes, which included loss of glial ensheathment of neuron cell bodies, increased neuronal cell death, and defects in animal behavior. Rescue experiments suggest that Spz3 can exert these effects only over very short distances. This work identifies essential roles for glial ensheathment of neuronal cell bodies in CNS homeostasis as well as Spz3 as a novel signaling factor required for maintenance of cortex glial morphology and neuron–glia contact.
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spelling pubmed-57334952018-04-15 The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function Coutinho-Budd, Jaeda C. Sheehan, Amy E. Freeman, Marc R. Genes Dev Research Paper Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron–glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of Drosophila cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia–soma interactions. We show that cortex glia tile with one another and with astrocytes to establish unique central nervous system (CNS) spatial domains that actively restrict glial growth, and selective ablation of cortex glia causes animal lethality. In an RNAi-based screen, we identified αSNAP (soluble NSF [N-ethylmalemeide-sensitive factor] attachment protein α) and several components of vesicle fusion and recycling machinery as essential for the maintenance of cortex glial morphology and continued contact with neurons. Interestingly, loss of the secreted neurotrophin Spätzle 3 (Spz3) phenocopied αSNAP phenotypes, which included loss of glial ensheathment of neuron cell bodies, increased neuronal cell death, and defects in animal behavior. Rescue experiments suggest that Spz3 can exert these effects only over very short distances. This work identifies essential roles for glial ensheathment of neuronal cell bodies in CNS homeostasis as well as Spz3 as a novel signaling factor required for maintenance of cortex glial morphology and neuron–glia contact. Cold Spring Harbor Laboratory Press 2017-10-15 /pmc/articles/PMC5733495/ /pubmed/29138279 http://dx.doi.org/10.1101/gad.305888.117 Text en © 2017 Coutinho-Budd et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Coutinho-Budd, Jaeda C.
Sheehan, Amy E.
Freeman, Marc R.
The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
title The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
title_full The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
title_fullStr The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
title_full_unstemmed The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
title_short The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
title_sort secreted neurotrophin spätzle 3 promotes glial morphogenesis and supports neuronal survival and function
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733495/
https://www.ncbi.nlm.nih.gov/pubmed/29138279
http://dx.doi.org/10.1101/gad.305888.117
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