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

Olivier Nicole, Donald M. Bell, Thierry Leste-Lasserre, Hélène Doat, François Guillemot, Emilie Pacary
Mol Psychiatry. 2018-04-30; :
DOI: 10.1038/s41380-018-0046-0

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1. Mol Psychiatry. 2018 Apr 30. doi: 10.1038/s41380-018-0046-0.

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
PMID: 29712998


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