Real‐time Recordings of Migrating Cortical Neurons from GFP and Cre Recombinase Expressing Mice

Tielens, Sylvia; Godin, Juliette D.; Nguyen, Laurent

doi:10.1002/0471142301.ns0329s74

Cited by 8 publications

(8 citation statements)

References 17 publications

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“…For time-lapse videomicroscopy, E16.5, embryo brains electroporated 2 days earlier, were dissected, embedded in 3% low-melt agarose (BioRad) diluted in HBSS (Hank’s Balanced Salt Solution, ThermoFisher Scientific) and sliced (300 µm) with a vibratome (Leica VT1000S, Leica Microsystems) 63 . Brain slices were cultured 16–24 h in semi-dry conditions (Millicell inserts, Merck Millipore), in a humidified incubator at 37 C in a 5% CO2 atmosphere in wells containing Neurobasal medium supplemented with 2% B27, 1% N2, and 1% penicillin/streptomycin (Gibco, Life Technologies).…”

Section: Methodsmentioning

confidence: 99%

TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis

et al. 2019

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De novo heterozygous missense variants in the γ-tubulin gene TUBG1 have been linked to human malformations of cortical development associated with intellectual disability and epilepsy. Here, we investigated through in-utero electroporation and in-vivo studies, how four of these variants affect cortical development. We show that TUBG1 mutants affect neuronal positioning, disrupting the locomotion of new-born neurons but without affecting progenitors’ proliferation. We further demonstrate that pathogenic TUBG1 variants are linked to reduced microtubule dynamics but without major structural nor functional centrosome defects in subject-derived fibroblasts. Additionally, we developed a knock-in Tubg1 Y92C/+ mouse model and assessed consequences of the mutation. Although centrosomal positioning in bipolar neurons is correct, they fail to initiate locomotion. Furthermore, Tubg1 Y92C/+ animals show neuroanatomical and behavioral defects and increased epileptic cortical activity. We show that Tubg1 Y92C/+ mice partially mimic the human phenotype and therefore represent a relevant model for further investigations of the physiopathology of cortical malformations.

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Section: Methodsmentioning

confidence: 99%

TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis

et al. 2019

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“…Electroporations of MGE were performed as previously described with minor modifications [62]. Briefly, endofree plasmid DNA solutions (2 µg/µl, Qiagen), mixed with 0.05% Fast Green (Sigma, St Louis, USA), were injected into the MGE of E13.5 brains slices or directly (ex vivo) into the MGE from E13.5 embryos.…”

Section: Electroporationmentioning

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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“…3). Such assays include live imaging of brain organotypic slices or explants to follow neuronal migration 102 , the Boyden chamber assay and microfluidic devices to study the migration of distinct cell types under the chemoattraction of selective molecules 5,18 . Interestingly, as novel biomaterials develop, these assays are increasingly being revisited as new tools for the study of neuronal migration.…”

Section: Understanding Cortical Cytoarchitectonicsmentioning

confidence: 99%

Cell migration promotes dynamic cellular interactions to control cerebral cortex morphogenesis

2019

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Cell migration controls key morphogenic events that shape the nervous system, ranging from neural tube closure to brain formation. During cerebral cortex development, cell migration is essential to set a precise temporal and spatial distribution pattern of neural cells that further engage in dynamic crosstalk to coordinate their maturation. Cerebral cortical activity relies on neural circuits formed of two main classes of neurons: excitatory projection neurons (PNs) that migrate along radial glia (RG) fibres within the cortex and inhibitory interneurons (INs) that originate from the ventral forebrain and reach the cortex along two stereotypical tangential routes 1. These neuronal classes include multiple subtypes for which proper laminar positioning and balanced integration into neural networks are determinant factors for cortical function. Cortical cytoarchitectonics reflects interplays between cell extrinsic cues and intrinsic mechanisms that coordinate the migration of neurons from their birthplace to a final destination, where they assemble into functional circuits. Most of these signals are involved in the control of cytoskeletal elements and their regulators to support dynamic shape changes underlying cell motility and allocation to ad hoc cortical layers 2. Migrating neurons not only receive important cues that direct their navigation and differentiation into the cortex but also influence morphogenetic events occurring in the vicinity of their migratory path. Recent reports have placed glia, and in particular microglia, the resident macrophage of the brain, as essential players for cortical morphogenesis via regulation of brain wiring and IN migration in the cortical wall. However, despite their prominent roles in cortical development, the migration pattern of the glial cells that transiently or permanently populate the cerebral cortex remains largely unexplored 3,4 Here, we review the migration strategies adopted by neural cells to navigate in the cortical wall and offer perspectives for the roles of cell migration in the formation of the cerebral cortex. We also discuss how bringing together quantitative experimental analyses with mathematical modelling fosters the discovery of new mechanisms of cortical morphogenesis 5. Furthermore, this Review sheds light on recent technological developments that advance our understanding of human cerebral cortical morphogenesis and help us decipher how cell migration deficits can interfere with this process in brain pathology. Cell migration in cortical development Cell migration is an important process that allows distinct cell types generated in different brain regions to settle in the cerebral cortex during embryogenesis. In mice, transient cell populations start colonizing the dorsal forebrain at embryonic day 10.5 (E10.5), and these cells guide the later migration and placement in the developing cortex of neurons generated between E11.5 and E18.5. In addition, most glial cells invade the cortical wall concurrently with neurons (Fig. 1a), with which some establish...

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Real‐time Recordings of Migrating Cortical Neurons from GFP and Cre Recombinase Expressing Mice

Cited by 8 publications

References 17 publications

TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis

TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis

Elongator controls cortical interneuron migration by regulating actomyosin dynamics

Cell migration promotes dynamic cellular interactions to control cerebral cortex morphogenesis

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