Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila

Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition...

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Main Authors: Marion Langen, Marta Koch, Jiekun Yan, Natalie De Geest, Maria-Luise Erfurth, Barret D Pfeiffer, Dietmar Schmucker, Yves Moreau, Bassem A Hassan
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2013-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/00337
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spelling doaj-258d5181d118405eb0d694e1b6c5a3052021-05-04T21:29:15ZengeLife Sciences Publications LtdeLife2050-084X2013-03-01210.7554/eLife.00337Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in DrosophilaMarion Langen0Marta Koch1Jiekun Yan2Natalie De Geest3Maria-Luise Erfurth4Barret D Pfeiffer5Dietmar Schmucker6Yves Moreau7Bassem A Hassan8Center for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Doctoral Program in Molecular and Cognitive Neuroscience, Doctoral School of Biomedical Sciences, University of Leuven, Leuven, BelgiumCenter for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, BelgiumCenter for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, BelgiumCenter for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, BelgiumVesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, University of Leuven School of Medicine, Leuven, BelgiumJanelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesVesalius Research Center, VIB, Leuven, Belgium; Department of Oncology, University of Leuven School of Medicine, Leuven, BelgiumDepartment of Electrical Engineering, University of Leuven, Leuven, BelgiumCenter for the Biology of Disease, VIB, Leuven, Belgium; Center for Human Genetics, University of Leuven School of Medicine, Leuven, Belgium; Doctoral Program in Molecular and Cognitive Neuroscience, Doctoral School of Biomedical Sciences, University of Leuven, Leuven, Belgium; Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, United StatesBrain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of neighboring postmitotic neurons during development regulates the robustness of axon target choice in a nondeterministic neuronal circuit. Specifically, neighboring postmitotic neurons communicate through Notch signaling during axonal targeting, to ensure balanced alternative axon target choices without a corresponding change in cell fate. Loss of Notch in postmitotic neurons modulates an axon's target choice. However, because neighboring axons respond by choosing the complementary target, the stereotyped connectivity pattern is preserved. In contrast, loss of Notch in clones of neighboring postmitotic neurons results in erroneous coinnervation by multiple axons. Our observations establish mutual inhibition of axonal target choice as a robustness mechanism for brain wiring and unveil a novel cell fate independent function for canonical Notch signaling.https://elifesciences.org/articles/00337NeurobiologyNeural CircuitRobustnessVariabilityNotch SignalingAxonal targeting
collection DOAJ
language English
format Article
sources DOAJ
author Marion Langen
Marta Koch
Jiekun Yan
Natalie De Geest
Maria-Luise Erfurth
Barret D Pfeiffer
Dietmar Schmucker
Yves Moreau
Bassem A Hassan
spellingShingle Marion Langen
Marta Koch
Jiekun Yan
Natalie De Geest
Maria-Luise Erfurth
Barret D Pfeiffer
Dietmar Schmucker
Yves Moreau
Bassem A Hassan
Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
eLife
Neurobiology
Neural Circuit
Robustness
Variability
Notch Signaling
Axonal targeting
author_facet Marion Langen
Marta Koch
Jiekun Yan
Natalie De Geest
Maria-Luise Erfurth
Barret D Pfeiffer
Dietmar Schmucker
Yves Moreau
Bassem A Hassan
author_sort Marion Langen
title Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
title_short Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
title_full Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
title_fullStr Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
title_full_unstemmed Mutual inhibition among postmitotic neurons regulates robustness of brain wiring in Drosophila
title_sort mutual inhibition among postmitotic neurons regulates robustness of brain wiring in drosophila
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2013-03-01
description Brain connectivity maps display a delicate balance between individual variation and stereotypy, suggesting the existence of dedicated mechanisms that simultaneously permit and limit individual variation. We show that during the development of the Drosophila central nervous system, mutual inhibition among groups of neighboring postmitotic neurons during development regulates the robustness of axon target choice in a nondeterministic neuronal circuit. Specifically, neighboring postmitotic neurons communicate through Notch signaling during axonal targeting, to ensure balanced alternative axon target choices without a corresponding change in cell fate. Loss of Notch in postmitotic neurons modulates an axon's target choice. However, because neighboring axons respond by choosing the complementary target, the stereotyped connectivity pattern is preserved. In contrast, loss of Notch in clones of neighboring postmitotic neurons results in erroneous coinnervation by multiple axons. Our observations establish mutual inhibition of axonal target choice as a robustness mechanism for brain wiring and unveil a novel cell fate independent function for canonical Notch signaling.
topic Neurobiology
Neural Circuit
Robustness
Variability
Notch Signaling
Axonal targeting
url https://elifesciences.org/articles/00337
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