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Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion

ABSTRACT: Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion

PROVIDER: PRJNA272678 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR1760950.fastq.gz	Fastqsanger.gz
	SRR1760960.fastq.gz	Fastqsanger.gz
	SRR1760970.fastq.gz	Fastqsanger.gz
	SRR1760951.fastq.gz	Fastqsanger.gz
	SRR1760961.fastq.gz	Fastqsanger.gz

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Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion

Project description:The evolutionary expansion of the human neocortex reflects increased amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis. Here, we analyze the transcriptomes of distinct progenitor subpopulations isolated by a novel approach from developing mouse and human neocortex. We identify 56 genes preferentially expressed in human apical and basal radial glia that lack mouse orthologs. Among these, ARHGAP11B has the highest degree of radial glia-specific expression. ARHGAP11B arose from partial duplication of the Rho GTPase-activating-protein–encoding ARHGAP11A on the human lineage after separation from the chimpanzee lineage. Expression of ARHGAP11B in embryonic mouse neocortex promotes basal progenitor generation and self-renewal, and can increase cortical plate area and induce gyrification. Hence, ARHGAP11B may have contributed to evolutionary expansion of human neocortex. Gene expression profiles of mouse and human purified neocortical progenitor types and neurons were generated by RNA-seq and analyzed including inter- and intra-species comparison.

2015-03-02 | E-GEOD-65000 | biostudies-arrayexpress

Human-specific gene ARHGAP11B promotes basal progenitor amplification and neocortex expansion

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Primate-expressed EPIREGULIN promotes basal progenitor proliferation in the developing neocortex

Project description:Neocortex expansion during evolution is linked to higher numbers of neurons thought to result from increased proliferative capacity and neurogenic potential of basal progenitors during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of both major basal progenitor types, intermediate basal progenitors and basal radial glia, whereas ablation of EPIREGULIN in human cortical organoids reduces basal progenitor proliferation. Here, we analyzed gene expression changes upon addition of EPIREGULIN to the mouse neocortex for 24 hours using hemisphere rotation culture. We performed fluorescent activated cell sorting to isolate radial glia (RG), intermediate progenitor (IP) cells and neurons (N) based on the nuclear markers Sox2 and Tbr2, and expression of GFP in neurons isolated from a Tubb3::GFP mouse reporter line.

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H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion by activating TRNP1 expression

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Sonic hedgehog signaling promotes basal radial glia and 1 intermediate progenitor cell

Project description:The unique mental abilities of humans are rooted in the immensely expanded and folded neocortex, which reflects the expansion of neural progenitors, especially basal progenitors including basalradial glia (bRGs, also called outer RGs) and intermediate progenitor cells (IPCs). Here, we show that constitutively active Shh signaling expanded basal progenitors and induced folding in the otherwise smooth mouse neocortex, whereas the loss of Shh signaling decreased the number of basal progenitors and the size of the neocortex. SHH signaling was strongly active in the human fetal neocortex but not in the mouse embryonic neocortex, and blocking SHH signaling in humancerebral organoids decreased the number of bRGs. Mechanistically, Shh signaling increased theinitial generation and self-renewal of bRGs as well as increasing IPC proliferation. Thus, robust SHH signaling in the human fetal neocortex may contribute to basal progenitor expansion and neocortical growth and folding.

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A novel population of Hopx-dependent human-like basal radial glial cells in the developing mouse neocortex

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A novel population of Hopx-dependent basal radial glial cells in the developing mouse neocortex

Project description:A specific subpopulation of neural progenitor cells, the basal radial glial cells (bRGCs) of the outer subventricular zone (OSVZ), are thought to have a key role in the evolutionary expansion of the mammalian neocortex. In the developing lissencephalic mouse neocortex, bRGCs exist at low abundance and show significant molecular differences from bRGCs in developing gyrencephalic species. Here, we demonstrate that the developing mouse medial neocortex (medNcx), in contrast to the canonically studied lateral neocortex (latNcx), exhibits an OSVZ and an abundance of bRGCs similar to that in developing gyrencephalic neocortex. Unlike bRGCs in developing mouse latNcx, the bRGCs in medNcx exhibit human bRGC-like gene expression, including expression of Hopx, a human bRGC marker. Disruption of Hopx expression in mouse embryonic medNcx and forced Hopx expression in mouse embryonic latNcx demonstrate that Hopx is required and sufficient, respectively, for a bRGC abundance as found in developing gyrencephalic neocortex. Taken together, our data identify a novel bRGC subpopulation in developing mouse medNcx that is highly related to bRGCs of developing gyrencephalic neocortex.

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