Cell Polarity in Cerebral Cortex Development—Cellular Architecture Shaped by Biochemical Networks

Hansen, Andi H.; Duellberg, Christian; Mieck, Christine; Loose, Martin; Hippenmeyer, Simon

doi:10.3389/fncel.2017.00176

Cited by 42 publications

(48 citation statements)

References 195 publications

(281 reference statements)

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“…We observed that the levels of filamentous (F) actin in primary dissociated cells, as indicated by phalloidin-rhodamine abundance, significantly decreased after mTOR inhibition or hyperactivation ( Figure 4A; n>7 cells/group from three independent experiments). The Rho GTPases, RHOA, RAC1 and CDC42, are actin regulators and prime candidate molecules to affect radial glial morphology and migration as Rho-ROCK signaling is required for oRG MST divisions (Hansen et al, 2017;Ostrem et al, 2014b) and CDC42 maintains radial glial polarity during mouse cortex development (Yokota et al, 2010). Dissociated primary oRG cells express CDC42, which decreases after treatment with rapamycin or BDNF, suggesting that optimal mTOR signaling maintains total CDC42 levels ( Figure 4C; n>3 cells/group from five independent experiments).…”

Section: Radial Fiber Truncation Following Mtor Dysregulation Is Rescmentioning

confidence: 99%

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

Andrews

Subramanian

Kriegstein

2020

Preprint

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Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. We find that dysregulation of mTOR signaling specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior. Thus, mTOR signaling can regulate the architecture of the developing human cortex by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold. Our study provides insight into how mTOR dysregulation may contribute to neurodevelopmental disease.

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Section: Radial Fiber Truncation Following Mtor Dysregulation Is Rescmentioning

confidence: 99%

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

Andrews

Subramanian

Kriegstein

2020

Preprint

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“…Through consecutive waves of neurogenesis, nascent neurons migrate radially along the RGP cell process into the most superficial layer of the developing cortex where they mature and differentiate. This process continues with each new wave of neurons migrating past the previous, resulting in the formation of distinct cortical laminae in an ‘inside‐out’ fashion . Early born, deep layer neurons (layers 5–6) are largely composed of corticofugal neurons that innervate brain regions beyond the neocortex including the thalamus, brainstem, and spinal cord .…”

Section: Radial Glia Progenitors Generating Cell Type Diversity In Thmentioning

confidence: 99%

Mechanisms of radial glia progenitor cell lineage progression

2017

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The mammalian cerebral cortex is responsible for higher cognitive functions such as perception, consciousness, and acquiring and processing information. The neocortex is organized into six distinct laminae, each composed of a rich diversity of cell types which assemble into highly complex cortical circuits. Radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. Here, we discuss recent discoveries emerging from clonal lineage analysis at the single RGP cell level that provide us with an inaugural quantitative framework of RGP lineage progression. We further discuss the importance of the relative contribution of intrinsic gene functions and non‐cell‐autonomous or community effects in regulating RGP proliferation behavior and lineage progression.

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“…We begin, however, with a brief summary of the key features of cortical development. For more in-depth reviews on this topic see Paridaen and Huttner (2014), Taverna et al (2014), Lodato and Arlotta (2015), Hansen et al (2017), and Huttner and Wieland (2019).…”

Section: Introductionmentioning

confidence: 99%

Adherens Junctions: Guardians of Cortical Development

Veeraval

O′Leary

Cooper

2020

Front. Cell Dev. Biol.

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Apical radial glia comprise the pseudostratified neuroepithelium lining the embryonic lateral ventricles and give rise to the extensive repertoire of pyramidal neuronal subtypes of the neocortex. The establishment of a highly apicobasally polarized radial glial morphology is a mandatory prerequisite for cortical development as it governs neurogenesis, neural migration and the integrity of the ventricular wall. As in all epithelia, cadherin-based adherens junctions (AJs) play an obligate role in the maintenance of radial glial apicobasal polarity and neuroepithelial cohesion. In addition, the assembly of resilient AJs is critical to the integrity of the neuroepithelium which must resist the tensile forces arising from increasing CSF volume and other mechanical stresses associated with the expansion of the ventricles in the embryo and neonate. Junctional instability leads to the collapse of radial glial morphology, disruption of the ventricular surface and cortical lamination defects due to failed neuronal migration. The fidelity of cortical development is therefore dependent on AJ assembly and stability. Mutations in genes known to control radial glial junction formation are causative for a subset of inherited cortical malformations (neuronal heterotopias) as well as perinatal hydrocephalus, reinforcing the concept that radial glial junctions are pivotal determinants of successful corticogenesis. In this review we explore the key animal studies that have revealed important insights into the role of AJs in maintaining apical radial glial morphology and function, and as such, have provided a deeper understanding of the aberrant molecular and cellular processes contributing to debilitating cortical malformations. We highlight the reciprocal interactions between AJs and the epithelial polarity complexes that impose radial glial apicobasal polarity. We also discuss the critical molecular networks promoting AJ assembly in apical radial glia and emphasize the role of the actin cytoskeleton in the stabilization of cadherin adhesion -a crucial factor in buffering the mechanical forces exerted as a consequence of cortical expansion.

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Cell Polarity in Cerebral Cortex Development—Cellular Architecture Shaped by Biochemical Networks

Cited by 42 publications

References 195 publications

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

mTOR signaling regulates the morphology and migration of outer radial glia in developing human cortex

Mechanisms of radial glia progenitor cell lineage progression

Adherens Junctions: Guardians of Cortical Development

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