A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration

O'Neill, Adam C; Kyrousi, Christina; Klaus, Johannes; Leventer, Richard J.; Kirk, Edwin P.; Fry, Andrew E.; Pilz, Daniela T.; Morgan, Tim; Jenkins, Zandra A.; Drukker, Micha; Berkovic, Samuel F.; Scheffer, Ingrid E.; Guerrini, Renzo; Markie, David; Götz, Magdalena; Cappello, Silvia; Robertson, Stephen

doi:10.1016/j.celrep.2018.11.029

Cited by 44 publications

(35 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rho signaling has been previously linked to RGC morphology, but how this was controlled rapidly and spatially was unknown. Global manipulation of GTPases disrupts filopodial activity in RGC basal structures, ultimately impairing neuronal migration and neurogenesis (Haubst et al, 2006;Li et al, 2008;Radakovits et al, 2009;Yokota et al, 2010) Further, RhoA cKO or disruption of a Rho modulator, PLEKHG6, impairs RGC organization and non-cell autonomously disrupts neuronal migration (Cappello et al, 2012;O'Neill et al, 2018). In neurons, RhoA inactivation increases branching, whereas RhoA activation reduces branching (Lee et al, 2000).…”

Section: Localized Rho-gtpase Signaling Controls Rgc Morphologymentioning

confidence: 99%

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Pilaz

Joshi

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

mRNA localization and local translation enable exquisite spatial and temporal control of gene expression, particularly in highly polarized and elongated cells. These features are especially prominent in radial glial cells (RGCs), which serve as neural and glial precursors of the developing cerebral cortex, and scaffolds for migrating neurons. Yet the mechanisms by which distinct sub-cellular compartments of RGCs accomplish their diverse functions are poorly understood. Here, we demonstrate that subcellular RNA localization and translation of the RhoGAP Arhgap11a controls RGC morphology and mediates cortical cytoarchitecture. Arhgap11a mRNA and protein exhibit conserved localization to RGC basal structures in mice and humans, conferred by a 5′UTR cis-element. Proper RGC morphology relies upon active Arhgap11a mRNA transport and localization to basal structures, where ARHGAP11A is locally synthesized. Thus, RhoA activity is spatially and acutely activated via local translation in RGCs to promote neuron positioning and cortical cytoarchitecture. Altogether, our study demonstrates that mRNA localization and local translation mediate compartmentalization of neural progenitor functions to control brain development.

show abstract

Section: Localized Rho-gtpase Signaling Controls Rgc Morphologymentioning

confidence: 99%

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Pilaz

Joshi

Liu

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…[99][100][101] As such, organoids have become exciting tools to examine the evolutionary cues that shape development of the brain, in particular for studies inspired by genetic analysis comparing humans to Neanderthals, chimpanzee, or other animals. [102][103][104][105]…”

Section: Organoids As An Emerging Technology For Analyzing the Human mentioning

confidence: 99%

Innovations in 3D Tissue Models of Human Brain Physiology and Diseases

Lovett

Nieland

Dingle

et al. 2020

Adv Funct Materials

View full text Add to dashboard Cite

3D laboratory tissue cultures have emerged as an alternative to traditional 2D culture systems that do not recapitulate native cell behavior. The discrepancy between in vivo and in vitro tissue-cell-molecular responses impedes understanding of human physiology in general and creates roadblocks for the discovery of therapeutic solutions. Two parallel approaches have emerged for the design of 3D culture systems. The first is biomedical engineering methodology, including bioengineered materials, bioprinting, microfluidics, and bioreactors, used alone or in combination, to mimic the microenvironments of native tissues. The second approach is organoid technology, in which stem cells are exposed to chemical and/or biological cues to activate differentiation programs that are reminiscent of human (prenatal) development. This review article describes recent technological advances in engineering 3D cultures that more closely resemble the human brain. The contributions of in vitro 3D tissue culture systems to new insights in neurophysiology, neurological diseases, and regenerative medicine are highlighted. Perspectives on designing improved tissue models of the human brain are offered, focusing on an integrative approach merging biomedical engineering tools with organoid biology.

show abstract

“…Li et al, 2017). In addition, abnormal neural migration, which occurs in genetic forms of lissencephaly and periventricular heterotopia, caused by mutations in genes, such as DCHS1, FAT4, or PLEKHG6, has been modeled in brain organoids (Bershteyn et al, 2017;O'Neill et al, 2018;Klaus et al, 2019).…”

Section: Modeling Human Neurological Disordersmentioning

confidence: 99%

Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids

Tian

Muffat

2020

J. Neurosci.

View full text Add to dashboard Cite

In vitro differentiation of pluripotent stem cells provides a systematic platform to study development and disease. Recent advances in brain organoid technology have created new opportunities to investigate the formation and function of the human brain, under physiological and pathological conditions. Brain organoids can be generated to model the cellular and structural development of the human brain, and allow the investigation of the intricate interactions between resident neural and glial cell types. Combined with new advances in gene editing, imaging, and genomic analysis, brain organoid technology can be applied to address questions pertinent to human brain development, disease, and evolution. However, the current iterations of brain organoids also have limitations in faithfully recapitulating the in vivo processes. In this perspective, we evaluate the recent progress in brain organoid technology, and discuss the experimental considerations for its utilization.

show abstract

A Primate-Specific Isoform of PLEKHG6 Regulates Neurogenesis and Neuronal Migration

Cited by 44 publications

References 75 publications

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Subcellular mRNA localization and local translation ofArhgap11ain radial glial cells regulates cortical development

Innovations in 3D Tissue Models of Human Brain Physiology and Diseases

Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids

Contact Info

Product

Resources

About