Plexin-B2 controls the timing of differentiation and the motility of cerebellar granule neurons

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Abstract

Plexin-B2 deletion leads to aberrant lamination of cerebellar granule neurons (CGNs) and Purkinje cells. Although in the cerebellum Plexin-B2 is only expressed by proliferating CGN precursors in the outer external granule layer (oEGL), its function in CGN development is still elusive. Here, we used 3D imaging, in vivo electroporation and live-imaging techniques to study CGN development in novel cerebellum-specific Plxnb2 conditional knockout mice. We show that proliferating CGNs in Plxnb2 mutants not only escape the oEGL and mix with newborn postmitotic CGNs. Furthermore, motility of mitotic precursors and early postmitotic CGNs is altered. Together, this leads to the formation of ectopic patches of CGNs at the cerebellar surface and an intermingling of normally time-stamped parallel fibers in the molecular layer (ML), and aberrant arborization of Purkinje cell dendrites. There results suggest that Plexin-B2 restricts CGN motility and might have a function in cytokinesis.

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All data generated or analysed during this study are included in the manuscript and supporting files

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Eljo Van Battum

Department of Development, Institut de la Vision, Paris, France

Competing interests
No competing interests declared.
Celine Heitz-Marchaland

Department of Development, Institut de la Vision, Paris, France

Competing interests
No competing interests declared.
Yvrick Zagar

Department of Development, Institut de la Vision, Paris, France

Competing interests
No competing interests declared.
Stéphane Fouquet

Department of Development, Institut de la Vision, Paris, France

Competing interests
No competing interests declared.
Rohini Kuner

Department of Pharmacology, Universität Heidelberg, Heidelberg, Germany

Competing interests
Rohini Kuner, Reviewing editor, eLife.
Alain Chédotal

Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06, INSERM, CNRS, Paris, France

For correspondence
alain.chedotal@inserm.fr

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0001-7577-3794

Funding

Agence Nationale de la Recherche (ANR-18-IAHU-01)

Alain Chédotal

Fondation pour la Recherche Médicale (CS 2018)

Alain Chédotal

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal housing, handling and experimental procedures were carried out in accordance to institutional guidelines, approved by the Sorbonne University ethic committee (Charles Darwin, permit 03787.02).

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.