A discrete subtype of neural progenitor crucial for cortical folding in the gyrencephalic mammalian brain.

Naoyuki Matsumoto,Toshihide Horiike,Hiroshi Kawasaki,Yohei Shinmyo,Satoshi Tanaka

doi:10.7554/elife.54873

Abstract

An increase in the diversity of neural progenitor subtypes and folding of the cerebral cortex are characteristic features which appeared during the evolution of the mammalian brain. Here, we show that the expansion of a specific subtype of neural progenitor is crucial for cortical folding. We found that outer radial glial (oRG) cells can be subdivided by HOPX expression in the gyrencephalic cerebral cortex of ferrets. Compared with HOPX-negative oRG cells, HOPX-positive oRG cells had high self-renewal activity and were accumulated in prospective gyral regions. Using our in vivo genetic manipulation technique for ferrets, we found that the number of HOPX-positive oRG cells and their self-renewal activity were regulated by sonic hedgehog (Shh) signaling. Importantly, suppressing Shh signaling reduced HOPX-positive oRG cells and cortical folding, while enhancing it had opposing effects. Our results reveal a novel subtype of neural progenitor important for cortical folding in gyrencephalic mammalian cerebral cortex.

Highlights

Crucial advances of the mammalian brain during evolution include the expansion and folding of the cerebral cortex (Molnar et al, 2006; Rakic, 2009)
To investigate the subtypes of neural progenitors in the outer SVZ (OSVZ), we performed triple immunostaining for Pax6, Tbr2 and HOPX using the developing ferret cerebral cortex at P1 (Figure 1A,B)
We have shown that outer radial glial (oRG) cells can be classified into two groups: HOPX-positive and HOPX-negative

Summary

Introduction

Crucial advances of the mammalian brain during evolution include the expansion and folding of the cerebral cortex (Molnar et al, 2006; Rakic, 2009). An increase in the diversity of neural progenitor subtypes is associated with the appearance of cortical folding during evolution (Dehay et al, 2015; Fernandez et al, 2016; Florio and Huttner, 2014; Kriegstein et al, 2006; Molnar et al, 2006; Rakic, 2009; Sun and Hevner, 2014). Neuroscience from increased numbers and diversity of neural progenitors (Dehay et al, 2015; Fernandez et al, 2016; Florio and Huttner, 2014; Kriegstein et al, 2006; Molnar et al, 2006; Rakic, 2009; Sun and Hevner, 2014), it has been difficult to test this proposal experimentally in vivo This is at least partially because of a paucity of rapid and efficient genetic manipulation techniques that could be applied to gyrencephalic brains. Our results reveal a novel subtype of neural progenitor important for cortical folding in the gyrencephalic mammalian cerebral cortex

Results

Discussion

Materials and methods