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

2018 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R. Long ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Progenitor Cell ◽  
Radial Glia ◽  
Specific Gene ◽  
Cell Type ◽  
Embryonic Mouse ◽  
Neuron Density ◽  
Developing Neocortex ◽  
Radial Dimension ◽  
Human Specific

AbstractThe evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. As a consequence, the postnatal ferret neocortex exhibits an increased neuron density in the upper cortical layers and expands in the radial dimension. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in developing ferret neocortex.

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

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R Long ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Progenitor Cell ◽  
Radial Glia ◽  
Specific Gene ◽  
Cell Type ◽  
Cortical Layers ◽  
Embryonic Mouse ◽  
Neuron Density ◽  
Developing Neocortex ◽  
Human Specific

The evolutionary increase in size and complexity of the primate neocortex is thought to underlie the higher cognitive abilities of humans. ARHGAP11B is a human-specific gene that, based on its expression pattern in fetal human neocortex and progenitor effects in embryonic mouse neocortex, has been proposed to have a key function in the evolutionary expansion of the neocortex. Here, we study the effects of ARHGAP11B expression in the developing neocortex of the gyrencephalic ferret. In contrast to its effects in mouse, ARHGAP11B markedly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, and results in extension of the neurogenic period and an increase in upper-layer neurons. Consequently, the postnatal ferret neocortex exhibits increased neuron density in the upper cortical layers and expands in both the radial and tangential dimensions. Thus, human-specific ARHGAP11B can elicit hallmarks of neocortical expansion in the developing ferret neocortex.

Human-specific ARHGAP11B increases size and folding of primate neocortex in the fetal marmoset

Science ◽  
2020 ◽  
Vol 369 (6503) ◽  
pp. 546-550 ◽  
Author(s):  
Michael Heide ◽  
Christiane Haffner ◽  
Ayako Murayama ◽  
Yoko Kurotaki ◽  
Haruka Shinohara ◽  
...  
Keyword(s):  
Subventricular Zone ◽  
Radial Glia ◽  
Common Marmoset ◽  
Primate Evolution ◽  
Specific Gene ◽  
Mammalian Evolution ◽  
Human Promoter ◽  
Neocortical Development ◽  
The Common ◽  
Human Specific

The neocortex has expanded during mammalian evolution. Overexpression studies in developing mouse and ferret neocortex have implicated the human-specific gene ARHGAP11B in neocortical expansion, but the relevance for primate evolution has been unclear. Here, we provide functional evidence that ARHGAP11B causes expansion of the primate neocortex. ARHGAP11B expressed in fetal neocortex of the common marmoset under control of the gene’s own (human) promoter increased the numbers of basal radial glia progenitors in the marmoset outer subventricular zone, increased the numbers of upper-layer neurons, enlarged the neocortex, and induced its folding. Thus, the human-specific ARHGAP11B drives changes in development in the nonhuman primate marmoset that reflect the changes in evolution that characterize human neocortical development.

scholarly journals Co-expression enrichment analysis at the single-cell level reveals convergent defects in neural progenitor cells and their cell-type transitions in neurodevelopmental disorders

2020 ◽  
Author(s):  
Kaifang Pang ◽  
Li Wang ◽  
Wei Wang ◽  
Jian Zhou ◽  
Chao Cheng ◽  
...  
Keyword(s):  
Single Cell ◽  
Neurodevelopmental Disorders ◽  
Progenitor Cell ◽  
Large Scale ◽  
Radial Glia ◽  
Neural Progenitor ◽  
Autism Spectrum ◽  
Cell Type ◽  
Sequencing Data ◽  
Cell Type Specific

AbstractRecent large-scale sequencing studies have identified a great number of genes whose disruptions cause neurodevelopmental disorders (NDDs). However, cell-type-specific functions of NDD genes and their contributions to NDD pathology are unclear. Here, we integrated NDD genetics with single-cell RNA sequencing data to identify cell-type and temporal convergence of genes involved in different NDDs. By assessing the co-expression enrichment pattern of various NDD gene sets, we identified mid-fetal cortical neural progenitor cell development—more specifically, ventricular radial glia-to-intermediate progenitor cell transition at gestational week 10—as a key convergent point in autism spectrum disorder (ASD) and epilepsy. Integrated gene ontology-based analyses further revealed that ASD genes function as upstream regulators to activate neural differentiation and inhibit cell cycle during the transition, whereas epilepsy genes function as downstream effectors in the same processes, offering a potential explanation for the high comorbidity rate of the two disorders. Together, our study provides a framework for investigating the cell-type-specific pathophysiology of NDDs.

scholarly journals Temporal and Spatial Transcriptomic Dynamics across Brain Development in Xenopus laevis tadpoles

2021 ◽  
Author(s):  
Aaron C Ta ◽  
Lin-Chien Huang ◽  
Caroline R McKeown ◽  
Jennifer E Bestman ◽  
Kendall Van Keuren-Jensen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Progenitor Cell ◽  
Neural Progenitor ◽  
Biological Processes ◽  
Cell Type ◽  
Mouse Development ◽  
Embryonic Mouse ◽  
Temporal And Spatial ◽  
The Brain

Abstract Amphibian metamorphosis is a transitional period that involves significant changes in the cell type populations and biological processes occurring in the brain. Analysis of gene expression dynamics during this process may provide insight into the molecular events underlying these changes. We conducted differential gene expression analyses of the developing X. laevis tadpole brain during this period in two ways: first, over stages of development in the midbrain, and second, across regions of the brain at a single developmental stage. We found that genes pertaining to positive regulation of neural progenitor cell proliferation as well as known progenitor cell markers were upregulated in the midbrain prior to metamorphic climax; concurrently, expression of cell cycle timing regulators decreased across this period, supporting the notion that cell cycle lengthening contributes to a decrease in proliferation by the end of metamorphosis. We also found that at the start of metamorphosis, neural progenitor populations appeared to be similar across the fore-, mid-, and hindbrain regions. Genes pertaining to negative regulation of differentiation were upregulated in the spinal cord compared to the rest of the brain, however, suggesting that a different program may regulate neurogenesis there. Finally, we found that regulation of biological processes like cell fate commitment and synaptic signaling follow similar trajectories in the brain across early tadpole metamorphosis and mid- to late-embryonic mouse development. By comparing expression across both temporal and spatial conditions, we have been able to illuminate cell type and biological pathway dynamics in the brain during metamorphosis.

scholarly journals A human-specific modifier of cortical circuit connectivity and function improves behavioral performance

2019 ◽  
Author(s):  
Ewoud R.E. Schmidt ◽  
Hanzhi T. Zhao ◽  
Jung M. Park ◽  
Jacob B. Dahan ◽  
Chris C. Rodgers ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Brain Evolution ◽  
Specific Gene ◽  
Behavioral Performance ◽  
Cortical Connectivity ◽  
Cortical Circuit ◽  
And Function ◽  
Circuit Function ◽  
And Behavior ◽  
Human Specific

SUMMARYThe remarkable cognitive abilities characterizing humans are thought to emerge from our unique features of cortical circuit architecture, including increased feedforward and feedback connectivity. However, our understanding of the evolutionary origin and nature of these changes in circuit connectivity, and how they impact cortical circuit function and behavior is currently lacking. Here, we demonstrate that expression of the human-specific gene duplication SRGAP2C leads to a specific increase in feedforward and feedback cortico-cortical connectivity. Moreover, humanized SRGAP2C mice display improved cortical sensory coding, and an enhanced ability to learn a cortex-dependent sensory discrimination task. Our results identify a novel substrate for human brain evolution whereby the emergence of SRGAP2C led to increased feedforward and feedback cortico-cortical connectivity, improved cortical sensory processing and enhanced behavioral performance.

scholarly journals Human-Specific Genes, Cortical Progenitor Cells, and Microcephaly

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1209
Author(s):  
Michael Heide ◽  
Wieland B. Huttner
Keyword(s):  
Cerebral Cortex ◽  
Cognitive Abilities ◽  
Functional Role ◽  
Brain Size ◽  
Cortical Development ◽  
Specific Gene ◽  
The Past ◽  
The Brain ◽  
Cortical Progenitor ◽  
Human Specific

Over the past few years, human-specific genes have received increasing attention as potential major contributors responsible for the 3-fold difference in brain size between human and chimpanzee. Accordingly, mutations affecting these genes may lead to a reduction in human brain size and therefore, may cause or contribute to microcephaly. In this review, we will concentrate, within the brain, on the cerebral cortex, the seat of our higher cognitive abilities, and focus on the human-specific gene ARHGAP11B and on the gene family comprising the three human-specific genes NOTCH2NLA, -B, and -C. These genes are thought to have significantly contributed to the expansion of the cerebral cortex during human evolution. We will summarize the evolution of these genes, as well as their expression and functional role during human cortical development, and discuss their potential relevance for microcephaly. Furthermore, we will give an overview of other human-specific genes that are expressed during fetal human cortical development. We will discuss the potential involvement of these genes in microcephaly and how these genes could be studied functionally to identify a possible role in microcephaly.

scholarly journals Single-cell delineation of lineage and genetic identity in the mouse brain

Nature ◽  
2021 ◽  
Author(s):  
Rachel C. Bandler ◽  
Ilaria Vitali ◽  
Ryan N. Delgado ◽  
May C. Ho ◽  
Elena Dvoretskova ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Progenitor Cell ◽  
Wide Spectrum ◽  
Cell Cycle Exit ◽  
Cell Type ◽  
Cell Level ◽  
Embryonic Mouse ◽  
Forebrain Development ◽  
Open Question ◽  
Lineage Divergence

AbstractDuring neurogenesis, mitotic progenitor cells lining the ventricles of the embryonic mouse brain undergo their final rounds of cell division, giving rise to a wide spectrum of postmitotic neurons and glia1,2. The link between developmental lineage and cell-type diversity remains an open question. Here we used massively parallel tagging of progenitors to track clonal relationships and transcriptomic signatures during mouse forebrain development. We quantified clonal divergence and convergence across all major cell classes postnatally, and found diverse types of GABAergic neuron that share a common lineage. Divergence of GABAergic clones occurred during embryogenesis upon cell-cycle exit, suggesting that differentiation into subtypes is initiated as a lineage-dependent process at the progenitor cell level.

scholarly journals Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex

2017 ◽  
Author(s):  
Marta Florio ◽  
Michael Heide ◽  
Holger Brandl ◽  
Anneline Pinson ◽  
Sylke Winkler ◽  
...  
Keyword(s):  
Human Evolution ◽  
Neural Progenitor Cell ◽  
Cell Type ◽  
Cell Type Specificity ◽  
Protein Coding ◽  
Neocortical Development ◽  
Human Genes ◽  
Stem And Progenitor Cells ◽  
Developing Neocortex ◽  
Human Specific

AbstractTo understand the molecular basis underlying the expansion of the neocortex during primate, and notably human, evolution, it is essential to identify the genes that are particularly active in the neural stem and progenitor cells of developing neocortex. Here, we have used existing transcriptome datasets to carry out a comprehensive screen for protein-coding genes preferentially expressed in progenitors of fetal human neocortex. In addition to the previously studied gene ARHGAP11B, we show that ten known and two newly identified human-specific genes exhibit such expression, however with distinct neural progenitor cell-type specificity compared to their ancestral paralogs. Furthermore, we identify 41 additional human genes with progenitor-enriched expression which have orthologs only in primates. Our study not only provides a resource of genes that are candidates to exert specific, and novel, roles in neocortical development, but also reveals that distinct mechanisms gave rise to these genes during primate, and notably human, evolution.

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