Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

Kalebic, Nereo; Gilardi, Carlotta; Albert, Mareike; Namba, Tsuneo; Long, Katherine R.; Kostić, Miloš; Langen, Barbara; Huttner, Wieland B.

doi:10.7554/elife.41241

Cited by 99 publications

(97 citation statements)

References 87 publications

(165 reference statements)

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“…Taken together, these results indicate that the human-specific gene ARHGAP11B, similar to results previously obtained in embryonic mouse (Florio et al, 2015), embryonic ferret (Kalebic et al, 2018) and fetal marmoset (Heide et al, 2020) neocortex, can substantially increase the abundance of cycling BPs in developing cerebral cortex-like tissue of our closest living relative, the chimpanzee.…”

Section: Increased Cycling Bp Abundance Upon Expression Of Human-specsupporting

confidence: 88%

“…ARHGAP11B is a human-specific gene (Dennis et al, 2017;Sudmant et al, 2010) and the first such gene to have been implicated in human neocortical development and evolution Florio et al, 2016;Heide et al, 2020;Kalebic et al, 2018). In fetal human neocortex, ARHGAP11B is preferentially expressed in cNPCs (Florio et al, 2015;Florio et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…In fetal human neocortex, ARHGAP11B is preferentially expressed in cNPCs (Florio et al, 2015;Florio et al, 2018). When 6 overexpressed in embryonic mouse and ferret neocortex, ARHGAP11B has been found to increase the proliferation and abundance of BPs (Florio et al, 2015;Kalebic et al, 2018), the cNPC class implicated in neocortical expansion during human development and evolution (Borrell & Götz, 2014;Dehay et al, 2015;Florio & Huttner, 2014;Lui et al, 2011). Moreover, a very recent study in which ARHGAP11B was expressed under the control of its own promoter to physiological levels in the fetal neocortex of the common marmoset has demonstrated that this human-specific gene can indeed induce the hallmarks of neocortical expansion in this nonhuman primate, increasing neocortex size, folding, BP levels and upper-layer neuron numbers (Heide et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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Human-specificARHGAP11Bis necessary and sufficient for human-type basal progenitor levels in primate brain organoids

Fischer

Peters

Namba

et al. 2020

Preprint

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Based on studies in various animal models, including developing ferret neocortex (Kalebic et al., 2018), the human-specific gene ARHGAP11B has been implicated in human neocortex expansion. However, the extent of its contribution to this expansion during primate evolution is unknown. Here we addressed this issue by genetic manipulation of ARHGAP11B levels and function in chimpanzee and human cerebral organoids. Interference with ARHGAP11B's function in human cerebral organoids caused a massive decrease, down to a chimpanzee level, in the proliferation and abundance of basal progenitors, the progenitors thought to have a key role in neocortex expansion. Conversely, ARHGAP11B expression in chimpanzee cerebral organoids resulted in a doubling of cycling basal progenitors. Taken together, our findings demonstrate that ARHGAP11B is necessary and sufficient to maintain the elevated basal progenitor levels that characterize the fetal human neocortex, suggesting that this human-specific gene was a major contributor to neocortex expansion during human evolution.

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Section: Increased Cycling Bp Abundance Upon Expression Of Human-specsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human-specificARHGAP11Bis necessary and sufficient for human-type basal progenitor levels in primate brain organoids

Fischer

Peters

Namba

et al. 2020

Preprint

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“…During evolution, a hominid-specific partial duplication of ARHGAP11A led to the emergence of ARHGAP11B, which has been linked to cerebral cortex expansion in humans. In the human developing cortex, ARHGAP11B is expressed in neural progenitors and its forcedexpression in developing mouse cortices, ferrets and marmosets promotes basal progenitor generation and neuron production (Florio et al, 2015;Heide et al, 2020;Kalebic et al, 2018). ARHGAP11B, however, lacks both the GTPase activity and the RNA motif for localizing to endfeet and indeed shows no subcellular localization in human cortices (Florio et al, 2018).…”

Section: Implications For Human Cortical Development and Diseasementioning

confidence: 99%

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

Pilaz

Joshi

Liu

et al. 2020

Preprint

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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.

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“…We hence focused on bRG-like cell production at mid-corticogenesis in Lis1 HET mouse mutants. bRG producing mechanisms have been associated with either alterations of mitosis spindle orientation leading to more oblique and vertical divisions (Kalebic et al, 2018; Liu et al, 2017; Wang et al, 2016; Wong et al, 2015), and/or to detachment from the apical surface via decreased cell adhesion (Ju et al, 2016; Martínez-Martínez et al, 2016; Narayanan et al, 2018; Tavano et al, 2018; Taverna et al, 2014). Many of the genes that were described to increase bRG-like cell generation induce more oblique divisions (Penisson et al, 2019), and mitotic spindle orientation is a well-described mechanism that may contribute to the fine tuning of aRG daughter cell fate (LaMonica et al, 2013; Taverna et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Lis1 mutation prevents basal radial glia-like cell production in the mouse

Penisson

Hirotsune

Francis

et al. 2020

Preprint

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Human cortical malformations are associated with progenitor proliferation and neuronal migration abnormalities. Progenitor cells include apical radial glia, intermediate progenitors and basal (or outer) radial glia (bRGs or oRGs). bRGs are few in number in lissencephalic species (e.g. the mouse) but abundant in gyrencephalic brains. The LIS1 gene coding for a dynein regulator, is mutated in human lissencephaly, associated also in some cases with microcephaly. LIS1 was shown to be important during cell division and neuronal migration. Here, we generated bRG-like cells in the mouse embryonic brain, investigating the role of Lis1 in their formation. This was achieved by in utero electroporation of a hominoid-specific gene TBC1D3 (coding for a RAB-GAP protein) at mouse embryonic day (E) 14.5. We first confirmed that TBC1D3 expression in wild-type (WT) brain generates numerous Pax6+ bRG-like cells that are basally localized. Second, using the same approach, we assessed the formation of these cells in heterozygote Lis1 mutant brains. Our novel results show that Lis1 depletion in the forebrain from E9.5 prevented subsequent TBC1D3-induced bRG-like cell amplification. Indeed, we observe disruption of the ventricular zone (VZ) in the mutant. Lis1 depletion altered adhesion proteins and mitotic spindle orientations at the ventricular surface and increased the proportion of abventricular mitoses. Progenitor outcome could not be further altered by TBC1D3. We conclude that perturbation of Lis1/LIS1 dosage is likely to be detrimental for appropriate progenitor number and position, contributing to lissencephaly pathogenesis.

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Human-specific ARHGAP11B induces hallmarks of neocortical expansion in developing ferret neocortex

Cited by 99 publications

References 87 publications

Human-specificARHGAP11Bis necessary and sufficient for human-type basal progenitor levels in primate brain organoids

Human-specificARHGAP11Bis necessary and sufficient for human-type basal progenitor levels in primate brain organoids

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

Lis1 mutation prevents basal radial glia-like cell production in the mouse

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