A novel role for CAMKIIβ in the regulation of cortical neuron migration: implications for neurodevelopmental disorders

1. Mol Psychiatry. 2018 Nov;23(11):2209-2226. doi: 10.1038/s41380-018-0046-0.
Epub 2018 Apr 30.

A novel role for CAMKIIβ in the regulation of cortical neuron migration:
implications for neurodevelopmental disorders.

Nicole O(1)(2), Bell DM(3), Leste-Lasserre T(4), Doat H(4), Guillemot F(5),
Pacary E(6)(7).

Author information:
(1)CNRS, UMR5293, Institut des Maladies Neurodégénératives, F-33000, Bordeaux,
France.
(2)Université de Bordeaux, F-33000, Bordeaux, France.
(3)Confocal and Image Analysis Facility, The Francis Crick Institute, 1 Midland
Road, London, NW1 1AT, UK.
(4)Transcriptome Facility, INSERM U1215, Neurocentre Magendie, F-33000,
Bordeaux, France.
(5)The Francis Crick Institute, 1 Midland Road, London, NW1 1AT, UK.
(6)Université de Bordeaux, F-33000, Bordeaux, France. .
(7)INSERM U1215, Neurocentre Magendie, F-33000, Bordeaux, France.
.

Perturbation of CaMKIIβ expression has been associated with multiple
neuropsychiatric diseases, highlighting CaMKIIβ as a gene of interest. Yet, in
contrast to CaMKIIα, the specific functions of CaMKIIβ in the brain remain
poorly explored. Here, we reveal a novel function for this CaMKII isoform in
vivo during neuronal development. By using in utero electroporation, we show
that CaMKIIβ is an important regulator of radial migration of projection neurons
during cerebral cortex development. Knockdown of CaMKIIβ causes accelerated
migration of nascent pyramidal neurons, whereas overexpression of CaMKIIβ
inhibits migration, demonstrating that precise regulation of CaMKIIβ expression
is required for correct neuronal migration. More precisely, CaMKIIβ controls the
multipolar-bipolar transition in the intermediate zone and locomotion in the
cortical plate through its actin-binding and -bundling activities. In addition,
our data indicate that a fine-tuned balance between CaMKIIβ and cofilin
activities is necessary to ensure proper migration of cortical neurons. Thus,
our findings define a novel isoform-specific function for CaMKIIβ, demonstrating
that CaMKIIβ has a major biological function in the developing brain.

DOI: 10.1038/s41380-018-0046-0
PMCID: PMC6129389
PMID: 29712998 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of Interest The authors declare no
conflict of interest.

Auteurs Bordeaux Neurocampus