During the development of the central nervous system (CNS), only motor axons project into peripheral nerves. Little is known about the cellular and molecular mechanisms, which control the development of a boundary at the CNS surface and prevent CNS neurons emigration from the neural tube. It was previously shown that a subset of spinal cord commissural axons abnormally invades sensory nerves in Ntn1 hypomorphic embryos and Dcc knockouts. However, whether netrin-1 also plays a similar role in the brain is unknown. In the hindbrain, precerebellar neurons migrate tangentially under the pial surface and their ventral migration is guided by netrin-1. Here, we show that pontine neurons and inferior olivary neurons, two types of precerebellar neurons, are not confined to the CNS in Ntn1 and Dcc mutant mice, but that they invade the trigeminal, auditory and vagus nerves. Using a Ntn1 conditional knockout, we show that netrin-1, released at the pial surface by ventricular zone progenitors is responsible for the CNS confinement of precerebellar neurons. We propose, that netrin-1 distribution sculpts the CNS boundary by keeping CNS neurons in netrin-1 rich-domains.
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01 January 2017
Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin-1
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Neural development
Juan Antonio Moreno-Bravo,
Juan Antonio Moreno-Bravo
†
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
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Sergi Roig Puiggros,
Sergi Roig Puiggros
†
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
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Heike Blockus,
Heike Blockus
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
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Chloé Dominici,
Chloé Dominici
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
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Pavol Zelina,
Pavol Zelina
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
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Patrick Mehlen,
Patrick Mehlen
2
Apoptosis, Cancer and Development Laboratory, Equipe labellisée ‘La Ligue’, LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France
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Alain Chédotal
Alain Chédotal
*
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
*Author for correspondence: alain.chedotal@inserm.fr
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Juan Antonio Moreno-Bravo
†
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
Sergi Roig Puiggros
†
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
Heike Blockus
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
Chloé Dominici
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
Pavol Zelina
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
Patrick Mehlen
2
Apoptosis, Cancer and Development Laboratory, Equipe labellisée ‘La Ligue’, LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France
Alain Chédotal
*
1
Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Institut de la Vision, 17 Rue Moreau, 75012 Paris, France
*Author for correspondence: alain.chedotal@inserm.fr
†
These authors contributed equally
Received:
14 Sep 2017
Accepted:
12 Dec 2017
Online ISSN: 1477-9129
Print ISSN: 0950-1991
Agence Nationale de la Recherche
(ANR-14-CE13-0004-01)
Development dev.159400.
Article history
Received:
14 Sep 2017
Accepted:
12 Dec 2017
Currently Viewing Accepted Manuscript - Newer Version Available
17 Jan 2018
Citation
Juan Antonio Moreno-Bravo, Sergi Roig Puiggros, Heike Blockus, Chloé Dominici, Pavol Zelina, Patrick Mehlen, Alain Chédotal; Commissural neurons transgress the CNS/PNS boundary in absence of ventricular zone-derived netrin-1. Development 2017; dev.159400. doi: https://doi.org/10.1242/dev.159400
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