Extracellular Control of Radial Glia Proliferation and Scaffolding During Cortical Development and Pathology

Ferent, Julien; Zaidi, Donia; Francis, Fiona

doi:10.3389/fcell.2020.578341

Cited by 28 publications

(21 citation statements)

References 281 publications

(359 reference statements)

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“…2) due to their migratory capacity, RG form scaffolds for migrating neurons and hence represent the pillars of cortex formation ( Borrell and Götz, 2014 ; Falk and Götz, 2017 ). As a consequence of disturbance of RG function during human brain development, neurodevelopmental disorders such as heterotopia and lissencephaly can develop ( Barkovich et al, 2005 ; Matsumoto et al, 2017 ; Ferent et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…After 24 h, the migrated cells exhibit the characteristic elongated RG-like morphology and express the RG-markers nestin and GFAP as well as the proliferation marker Ki-67 ( Figure 3A ). In vivo , RG are highly polarized and have a particular elongated morphology since they form processes extending from the apical to the basal side of the cortex ( Ferent et al, 2020 ). In accordance with that, the nestin- and GFAP-positive cells migrating out of the hNPC sphere core display an active growth cone protrusion which diverges from the cell body to explore the vicinal environment ( Figure 3A ; Baumann et al (2015) ).…”

Section: Resultsmentioning

confidence: 99%

“…The migratory potential of the hNPC-derived RG is preserved in vitro over the time-course of at least 120 h ( Figure 3B ). However, a decrease in migration speed can be observed after the first 24 h. Since the specific RG architecture provides a scaffold supporting neuronal migration during cortex development, the correct formation and maintenance of the RG scaffold is crucial for the organization of neuronal networks and disturbances correlate with cortical malformations such as human lissencephaly, polymicrogyria and heterotopia ( Ferent et al, 2020 ). Therefore, RG migration (NPC2) is a fundamental neurodevelopmental key event, which is indispensable in a predictive testing battery identifying chemical-induced DNT.…”

Section: Resultsmentioning

confidence: 99%

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Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

et al. 2022

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There is a call for a paradigm shift in developmental neurotoxicity (DNT) evaluation, which demands the implementation of faster, more cost-efficient, and human-relevant test systems than current in vivo guideline studies. Under the umbrella of the Organisation for Economic Co-operation and Development (OECD), a guidance document is currently being prepared that instructs on the regulatory use of a DNT in vitro battery (DNT IVB) for fit-for-purpose applications. One crucial issue for OECD application of methods is validation, which for new approach methods (NAMs) requires novel approaches. Here, mechanistic information previously identified in vivo, as well as reported neurodevelopmental adversities in response to disturbances on the cellular and tissue level, are of central importance. In this study, we scientifically validate the Neurosphere Assay, which is based on human primary neural progenitor cells (hNPCs) and an integral part of the DNT IVB. It assesses neurodevelopmental key events (KEs) like NPC proliferation (NPC1ab), radial glia cell migration (NPC2a), neuronal differentiation (NPC3), neurite outgrowth (NPC4), oligodendrocyte differentiation (NPC5), and thyroid hormone-dependent oligodendrocyte maturation (NPC6). In addition, we extend our work from the hNPCs to human induced pluripotent stem cell-derived NPCs (hiNPCs) for the NPC proliferation (iNPC1ab) and radial glia assays (iNPC2a). The validation process we report for the endpoints studied with the Neurosphere Assays is based on 1) describing the relevance of the respective endpoints for brain development, 2) the confirmation of the cell type-specific morphologies observed in vitro, 3) expressions of cell type-specific markers consistent with those morphologies, 4) appropriate anticipated responses to physiological pertinent signaling stimuli and 5) alterations in specific in vitro endpoints upon challenges with confirmed DNT compounds. With these strong mechanistic underpinnings, we posit that the Neurosphere Assay as an integral part of the DNT in vitro screening battery is well poised for DNT evaluation for regulatory purposes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

et al. 2022

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“…Various signaling pathways are involved in promoting proliferation of neural progenitor cells. Notch, Shh, Wnt, PDGF, FGF, ECM-integrin, ERK, Hippo, PI3K-AKT, and mTOR are some of the most notable examples ( Penisson et al, 2019 ; Ferent et al, 2020 ; Kalebic and Huttner, 2020 ). Many of the components of those pathways have been implicated in MCDs.…”

Section: Cell Biological Basis Of Malformations Of Cortical Development In Neural Progenitorsmentioning

confidence: 99%

Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells

Ossola

Kalebic

2022

Front. Neurosci.

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The cerebral cortex is a structure that underlies various brain functions, including cognition and language. Mammalian cerebral cortex starts developing during the embryonic period with the neural progenitor cells generating neurons. Newborn neurons migrate along progenitors’ radial processes from the site of their origin in the germinal zones to the cortical plate, where they mature and integrate in the forming circuitry. Cell biological features of neural progenitors, such as the location and timing of their mitoses, together with their characteristic morphologies, can directly or indirectly regulate the abundance and the identity of their neuronal progeny. Alterations in the complex and delicate process of cerebral cortex development can lead to malformations of cortical development (MCDs). They include various structural abnormalities that affect the size, thickness and/or folding pattern of the developing cortex. Their clinical manifestations can entail a neurodevelopmental disorder, such as epilepsy, developmental delay, intellectual disability, or autism spectrum disorder. The recent advancements of molecular and neuroimaging techniques, along with the development of appropriate in vitro and in vivo model systems, have enabled the assessment of the genetic and environmental causes of MCDs. Here we broadly review the cell biological characteristics of neural progenitor cells and focus on those features whose perturbations have been linked to MCDs.

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“…The primary cilium is an organelle that protrudes from the apical plasma membrane of APs into the lumen of the ventricle, and that plays a crucial role in progenitor fate specification and neurogenesis [ 30 , 31 ]. Embryonic CSF contains a variety of secreted (or released) factors that have established roles in cortical development [ 32 ]. These factors act through binding to specific receptors expressed on the primary cilium plasma membrane to regulate the cell biology and behavior of APs.…”

Section: Principal Classes Of Npcsmentioning

confidence: 99%

How neural stem cells contribute to neocortex development

Xing

Wilsch‐Bräuninger

Huttner

2021

Biochemical Society Transactions

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The mammalian neocortex is the seat of higher cognitive functions, such as thinking and language in human. A hallmark of the neocortex are the cortical neurons, which are generated from divisions of neural progenitor cells (NPCs) during development, and which constitute a key feature of the well-organized layered structure of the neocortex. Proper formation of neocortex structure requires an orchestrated cellular behavior of different cortical NPCs during development, especially during the process of cortical neurogenesis. Here, we review the great diversity of NPCs and their contribution to the development of the neocortex. First, we review the categorization of NPCs into different classes and types based on their cell biological features, and discuss recent advances in characterizing marker expression and cell polarity features in the different types of NPCs. Second, we review the different modes of cell divisions that NPCs undergo and discuss the importance of the balance between proliferation and differentiation of NPCs in neocortical development. Third, we review the different proliferative capacities among different NPC types and among the same type of NPC in different mammalian species. Dissecting the differences between NPC types and differences among mammalian species is beneficial to further understand the development and the evolutionary expansion of the neocortex and may open up new therapeutic avenues for neurodevelopmental and psychiatric disorders.

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Extracellular Control of Radial Glia Proliferation and Scaffolding During Cortical Development and Pathology

Cited by 28 publications

References 281 publications

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

Scientific Validation of Human Neurosphere Assays for Developmental Neurotoxicity Evaluation

Roots of the Malformations of Cortical Development in the Cell Biology of Neural Progenitor Cells

How neural stem cells contribute to neocortex development

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