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

ABSTRACT: Perturbation of CaMKII? expression has been associated with multiple neuropsychiatric diseases, highlighting CaMKII? as a gene of interest. Yet, in contrast to CaMKII?, the specific functions of CaMKII? 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 CaMKII? is an important regulator of radial migration of projection neurons during cerebral cortex development. Knockdown of CaMKII? causes accelerated migration of nascent pyramidal neurons, whereas overexpression of CaMKII? inhibits migration, demonstrating that precise regulation of CaMKII? expression is required for correct neuronal migration. More precisely, CaMKII? 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 CaMKII? and cofilin activities is necessary to ensure proper migration of cortical neurons. Thus, our findings define a novel isoform-specific function for CaMKII?, demonstrating that CaMKII? has a major biological function in the developing brain.

SUBMITTER: Nicole O

PROVIDER: S-EPMC6129389 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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

Nicole Olivier O Bell Donald M DM Leste-Lasserre Thierry T Doat Hélène H Guillemot François F Pacary Emilie E

Molecular psychiatry 20180430 11

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. Knockd ...[more]

PMID: 29712998

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Project description:Macroautophagy/autophagy is an evolutionarily highly conserved catabolic process that is important for the clearance of cytosolic contents to maintain cellular homeostasis and survival. Recent findings point toward a critical role for autophagy in brain function, not only by preserving neuronal health, but especially by controlling different aspects of neuronal development and functioning. In line with this, mutations in autophagy-related genes are linked to various key characteristics and symptoms of neurodevelopmental disorders (NDDs), including autism, micro-/macrocephaly, and epilepsy. However, the group of NDDs caused by mutations in autophagy-related genes is relatively small. A significant proportion of NDDs are associated with mutations in genes encoding epigenetic regulatory proteins that modulate gene expression, so-called chromatinopathies. Intriguingly, several of the NDD-linked chromatinopathy genes have been shown to regulate autophagy-related genes, albeit in non-neuronal contexts. From these studies it becomes evident that tight transcriptional regulation of autophagy-related genes is crucial to control autophagic activity. This opens the exciting possibility that aberrant autophagic regulation might underly nervous system impairments in NDDs with disturbed epigenetic regulation. We here summarize NDD-related chromatinopathy genes that are known to regulate transcriptional regulation of autophagy-related genes. Thereby, we want to highlight autophagy as a candidate key hub mechanism in NDD-related chromatinopathies.Abbreviations: ADNP: activity dependent neuroprotector homeobox; ASD: autism spectrum disorder; ATG: AutTophaGy related; CpG: cytosine-guanine dinucleotide; DNMT: DNA methyltransferase; EHMT: euchromatic histone lysine methyltransferase; EP300: E1A binding protein p300; EZH2: enhancer of zeste 2 polycomb repressive complex 2 subunit; H3K4me3: histone 3 lysine 4 trimethylation; H3K9me1/2/3: histone 3 lysine 9 mono-, di-, or trimethylation; H3K27me2/3: histone 3 lysine 27 di-, or trimethylation; hiPSCs: human induced pluripotent stem cells; HSP: hereditary spastic paraplegia; ID: intellectual disability; KANSL1: KAT8 regulatory NSL complex subunit 1; KAT8: lysine acetyltransferase 8; KDM1A/LSD1: lysine demethylase 1A; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin complex 1; NDD: neurodevelopmental disorder; PHF8: PHD finger protein 8; PHF8-XLID: PHF8-X linked intellectual disability syndrome; PTM: post-translational modification; SESN2: sestrin 2; YY1: YY1 transcription factor; YY1AP1: YY1 associated protein 1.

Dataset Information

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

Publications

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

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