MicroRNA Targeting of CoREST Controls Polarization of Migrating Cortical Neurons

Volvert, Marie-Laure; Prévôt, Pierre-Paul; Close, Pierre; Laguesse, Sophie; Pirotte, Sophie; Hemphill, James; Rogister, Florence; Kruzy, Nathalie; Sacheli, Rosalie; Moonen, Gustave; Deiters, Alexander; Merkenschlager, Matthias; Chariot, Alain; Malgrange, Brigitte; Godin, Juliette D.; Nguyen, Laurent

doi:10.1016/j.celrep.2014.03.075

Cited by 66 publications

(70 citation statements)

References 64 publications

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“…During cortex development in rat, for example, a bipolarto-multipolar transformation of neural progenitor cells occurs when they reach the intermediate zone; another transformation -back to a bipolar morphology -is required for the subsequent glia-guided locomotion of these cells in the cortical plate (Noctor et al, 2004). Notably, Dicer1 deletion at this stage inhibits the conversion of neurons from a multipolar to a bipolar shape during migration (Volvert et al, 2014), suggesting an involvement of miRNAs in neuronal polarization (Fig. 2C).…”

Section: Neuronal Polarization Axon Pathfinding and Dendritogenesismentioning

confidence: 96%

“…in the case of miR-134; Gaughwin et al, 2011) or indirectly by targeting members of the CoREST/REST transcriptional repressor complex (e.g. in the case of miR-22 and miR-124; Volvert et al, 2014). In these studies, elevated levels of miR-134, miR-22 or miR-124 attenuated neuronal migration by downregulating Dcx expression.…”

Section: Migrationmentioning

confidence: 98%

“…2C). In addition, the re-introduction of miR-22 and miR-214 restores the multipolar-to-bipolar conversion, arguing for a particularly important role for these two specific miRNAs in polarization (Volvert et al, 2014).…”

Section: Neuronal Polarization Axon Pathfinding and Dendritogenesismentioning

confidence: 99%

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MicroRNAs in neural development: from master regulators to fine-tuners

2017

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The proper formation and function of neuronal networks is required for cognition and behavior. Indeed, pathophysiological states that disrupt neuronal networks can lead to neurodevelopmental disorders such as autism, schizophrenia or intellectual disability. It is wellestablished that transcriptional programs play major roles in neural circuit development. However, in recent years, post-transcriptional control of gene expression has emerged as an additional, and probably equally important, regulatory layer. In particular, it has been shown that microRNAs (miRNAs), an abundant class of small regulatory RNAs, can regulate neuronal circuit development, maturation and function by controlling, for example, local mRNA translation. It is also becoming clear that miRNAs are frequently dysregulated in neurodevelopmental disorders, suggesting a role for miRNAs in the etiology and/or maintenance of neurological disease states. Here, we provide an overview of the most prominent regulatory miRNAs that control neural development, highlighting how they act as 'master regulators' or 'fine-tuners' of gene expression, depending on context, to influence processes such as cell fate determination, cell migration, neuronal polarization and synapse formation.

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Section: Neuronal Polarization Axon Pathfinding and Dendritogenesismentioning

confidence: 96%

Section: Migrationmentioning

confidence: 98%

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MicroRNAs in neural development: from master regulators to fine-tuners

2017

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“…Indeed, when analyzed at E14.5, projection neurons migrate radially predominantly via locomotion on radial glia cell (RGC) fibers. This locomotion of projection neurons along RGC fibers requires a more stable morphology that mostly involves MT regulation by its associated proteins [15,56,57]. In contrast, interneurons migrate tangentially, mostly relying on actomyosin dynamics to support nucleokinesis, dynamic branching of their leading process [10,11,53,58] and their direction of migration [59].…”

Section: Multiple Roles For Elongator During the Establishment Of Thementioning

confidence: 99%

Elongator controls cortical interneuron migration by regulating actomyosin dynamics

et al. 2016

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The migration of cortical interneurons is a fundamental process for the establishment of cortical connectivity and its impairment underlies several neurological disorders. During development, these neurons are born in the ganglionic eminences and they migrate tangentially to populate the cortical layers. This process relies on various morphological changes that are driven by dynamic cytoskeleton remodelings. By coupling time lapse imaging with molecular analyses, we show that the Elongator complex controls cortical interneuron migration in mouse embryos by regulating nucleokinesis and branching dynamics. At the molecular level, Elongator fine-tunes actomyosin forces by regulating the distribution and turnover of actin microfilaments during cell migration. Thus, we demonstrate that Elongator cell-autonomously promotes cortical interneuron migration by controlling actin cytoskeletal dynamics.

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“…[24][25][26] It was previously shown that neuronal migration defects can affect the multipolar-bipolar transition of cortical neurons which is important for correct placement of these cells within the cortex. 27 Due to the finding that miR-338 has the capacity to influence the migration of neurons toward the CP, we examined whether modulation of miR-338 expression alters the morphology of neurons within the CP.…”

Section: Mir-338 Affects Neuronal Morphologies and Polarity In Vivomentioning

confidence: 99%

MicroRNA-338 modulates cortical neuronal placement and polarity

et al. 2017

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The precise spatial and temporal regulation of gene expression orchestrates the many intricate processes during brain development. In the present study we examined the role of the brain-enriched microRNA-338 (miR-338) during mouse cortical development. Reduction of miR-338 levels in the developing mouse cortex, using a sequence-specific miR-sponge, resulted in a loss of neuronal polarity in the cortical plate and significantly reduced the number of neurons within this cortical layer. Conversely, miR-338 overexpression in developing mouse cortex increased the number of neurons, which exhibited a multipolar morphology. All together, our results raise the possibility for a direct role for this non-coding RNA, which was recently associated with schizophrenia, in the regulation of cortical neuronal polarity and layer placement.

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MicroRNA Targeting of CoREST Controls Polarization of Migrating Cortical Neurons

Cited by 66 publications

References 64 publications

MicroRNAs in neural development: from master regulators to fine-tuners

MicroRNAs in neural development: from master regulators to fine-tuners

Elongator controls cortical interneuron migration by regulating actomyosin dynamics

MicroRNA-338 modulates cortical neuronal placement and polarity

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