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Genetic Dissection of the Function of Hindbrain Axonal Commissures

In Bilateria, many axons cross the midline of the central nervous system, forming well-defined commissures. Whereas in mammals the functions of commissures in the forebrain and in the visual system are well established, functions at other axial levels are less clearly understood. Here, we have disse...

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Autores principales: Renier, Nicolas, Schonewille, Martijn, Giraudet, Fabrice, Badura, Aleksandra, Tessier-Lavigne, Marc, Avan, Paul, De Zeeuw, Chris I., Chédotal, Alain
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834709/
https://www.ncbi.nlm.nih.gov/pubmed/20231872
http://dx.doi.org/10.1371/journal.pbio.1000325
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author Renier, Nicolas
Schonewille, Martijn
Giraudet, Fabrice
Badura, Aleksandra
Tessier-Lavigne, Marc
Avan, Paul
De Zeeuw, Chris I.
Chédotal, Alain
author_facet Renier, Nicolas
Schonewille, Martijn
Giraudet, Fabrice
Badura, Aleksandra
Tessier-Lavigne, Marc
Avan, Paul
De Zeeuw, Chris I.
Chédotal, Alain
author_sort Renier, Nicolas
collection PubMed
description In Bilateria, many axons cross the midline of the central nervous system, forming well-defined commissures. Whereas in mammals the functions of commissures in the forebrain and in the visual system are well established, functions at other axial levels are less clearly understood. Here, we have dissected the function of several hindbrain commissures using genetic methods. By taking advantage of multiple Cre transgenic lines, we have induced site-specific deletions of the Robo3 receptor. These lines developed with the disruption of specific commissures in the sensory, motor, and sensorimotor systems, resulting in severe and permanent functional deficits. We show that mice with severely reduced commissures in rhombomeres 5 and 3 have abnormal lateral eye movements and auditory brainstem responses, respectively, whereas mice with a primarily uncrossed climbing fiber/Purkinje cell projection are strongly ataxic. Surprisingly, although rerouted axons remain ipsilateral, they still project to their appropriate neuronal targets. Moreover, some Cre;Robo3 lines represent potential models that can be used to study human syndromes, including horizontal gaze palsy with progressive scoliosis (HGPPS). To our knowledge, this study is one of the first to link defects in commissural axon guidance with specific cellular and behavioral phenotypes.
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spelling pubmed-28347092010-03-16 Genetic Dissection of the Function of Hindbrain Axonal Commissures Renier, Nicolas Schonewille, Martijn Giraudet, Fabrice Badura, Aleksandra Tessier-Lavigne, Marc Avan, Paul De Zeeuw, Chris I. Chédotal, Alain PLoS Biol Research Article In Bilateria, many axons cross the midline of the central nervous system, forming well-defined commissures. Whereas in mammals the functions of commissures in the forebrain and in the visual system are well established, functions at other axial levels are less clearly understood. Here, we have dissected the function of several hindbrain commissures using genetic methods. By taking advantage of multiple Cre transgenic lines, we have induced site-specific deletions of the Robo3 receptor. These lines developed with the disruption of specific commissures in the sensory, motor, and sensorimotor systems, resulting in severe and permanent functional deficits. We show that mice with severely reduced commissures in rhombomeres 5 and 3 have abnormal lateral eye movements and auditory brainstem responses, respectively, whereas mice with a primarily uncrossed climbing fiber/Purkinje cell projection are strongly ataxic. Surprisingly, although rerouted axons remain ipsilateral, they still project to their appropriate neuronal targets. Moreover, some Cre;Robo3 lines represent potential models that can be used to study human syndromes, including horizontal gaze palsy with progressive scoliosis (HGPPS). To our knowledge, this study is one of the first to link defects in commissural axon guidance with specific cellular and behavioral phenotypes. Public Library of Science 2010-03-09 /pmc/articles/PMC2834709/ /pubmed/20231872 http://dx.doi.org/10.1371/journal.pbio.1000325 Text en Renier et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Renier, Nicolas
Schonewille, Martijn
Giraudet, Fabrice
Badura, Aleksandra
Tessier-Lavigne, Marc
Avan, Paul
De Zeeuw, Chris I.
Chédotal, Alain
Genetic Dissection of the Function of Hindbrain Axonal Commissures
title Genetic Dissection of the Function of Hindbrain Axonal Commissures
title_full Genetic Dissection of the Function of Hindbrain Axonal Commissures
title_fullStr Genetic Dissection of the Function of Hindbrain Axonal Commissures
title_full_unstemmed Genetic Dissection of the Function of Hindbrain Axonal Commissures
title_short Genetic Dissection of the Function of Hindbrain Axonal Commissures
title_sort genetic dissection of the function of hindbrain axonal commissures
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2834709/
https://www.ncbi.nlm.nih.gov/pubmed/20231872
http://dx.doi.org/10.1371/journal.pbio.1000325
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