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

Nereo Kalebic,Takashi Namba,Mareike Albert,Katherine R Long,Barbara Langen,Milos Kostic,Wieland B Huttner,Carlotta Gilardi

doi:10.7554/elife.41241

Nereo Kalebic, Takashi Namba + Show 6 more

Open Access

https://doi.org/10.7554/elife.41241

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Abstract

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.

Highlights

The expansion of the neocortex during primate evolution is thought to constitute one important basis for the unparalleled cognitive abilities of humans
Two major classes of neural progenitors can be distinguished: apical progenitors (APs), whose cell bodies reside in the ventricular zone (VZ), and basal progenitors (BPs), whose cell bodies reside in the subventricular zone (SVZ)
We expressed ARHGAP11B in the ferret neocortex starting at embryonic day 33 (E33), when both the generation of upper-layer neurons and formation of the OSVZ start (Martınez-Martınez et al, 2016)

Summary

Introduction

The expansion of the neocortex during primate evolution is thought to constitute one important basis for the unparalleled cognitive abilities of humans. The evolutionary expansion of the neocortex is characteristically accompanied by an increase in the abundance of proliferative bRG, in the length of the neurogenic period, and in the relative proportion of upper-layer neurons within the cortical plate (Borrell and Gotz, 2014; Dehay et al, 2015; Florio and Huttner, 2014; Geschwind and Rakic, 2013; Lui et al, 2011; Molnar et al, 2006; Sousa et al, 2017; Wilsch-Brauninger et al, 2016) This is most obvious when comparing extant rodents, such as mouse, with primates, such as human.

Results

E33 ARHGAP11B

F Layers II-IV thickness

Discussion

Materials and methods

Funding Funder European Molecular Biology Organization