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 ◽  
...  

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.


2011 ◽  
Vol 22 (2) ◽  
pp. 469-481 ◽  
Author(s):  
Iva Kelava ◽  
Isabel Reillo ◽  
Ayako Y. Murayama ◽  
Alex T. Kalinka ◽  
Denise Stenzel ◽  
...  


Development ◽  
2021 ◽  
Vol 148 (4) ◽  
pp. dev189191
Author(s):  
Toshiyuki Ohtsuka ◽  
Ryoichiro Kageyama

ABSTRACTNeural stem cells (NSCs) gradually alter their characteristics during mammalian neocortical development, resulting in the production of various neurons and glial cells, and remain in the postnatal brain as a source of adult neurogenesis. Notch-Hes signaling is a key regulator of stem cell properties in the developing and postnatal brain, and Hes1 is a major effector that strongly inhibits neuronal differentiation and maintains NSCs. To manipulate Hes1 expression levels in NSCs, we generated transgenic (Tg) mice using the Tet-On system. In Hes1-overexpressing Tg mice, NSCs were maintained in both embryonic and postnatal brains, and generation of later-born neurons was prolonged until later stages in the Tg neocortex. Hes1 overexpression inhibited the production of Tbr2+ intermediate progenitor cells but instead promoted the generation of basal radial glia-like cells in the subventricular zone (SVZ) at late embryonic stages. Furthermore, Hes1-overexpressing Tg mice exhibited the expansion of NSCs and enhanced neurogenesis in the SVZ of adult brain. These results indicate that Hes1 overexpression expanded the embryonic NSC pool and led to the expansion of the NSC reservoir in the postnatal and adult brain.



2018 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R. Long ◽  
...  

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.



2020 ◽  
Author(s):  
Jan Fischer ◽  
Jula Peters ◽  
Takashi Namba ◽  
Wieland B. Huttner ◽  
Michael Heide

AbstractBased 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.



Author(s):  
Sascha Knauf ◽  
Sophie Seehase ◽  
Simone Switalla ◽  
Vanessa Neuhaus ◽  
Martina Zoeller ◽  
...  


eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Nereo Kalebic ◽  
Carlotta Gilardi ◽  
Mareike Albert ◽  
Takashi Namba ◽  
Katherine R Long ◽  
...  

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.



2000 ◽  
Vol 114 (1) ◽  
pp. 3-17 ◽  
Author(s):  
P. Collins ◽  
L. S. Wilkinson ◽  
B. J. Everitt ◽  
T. W. Robbins ◽  
A. C. Roberts


Author(s):  
Ian Richard Phillips
Keyword(s):  


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