How Cells Fold the Cerebral Cortex

Abstract

Folding of the cerebral cortex is as highly intriguing as poorly understood. At first sight, this may appear as simple tissue crumpling inside an excessively small cranium, but the process is clearly much more complex and developmentally predetermined. Whereas theoretical modeling supports a critical role for biomechanics, experimental evidence demonstrates the fundamental role of specific progenitor cell types, cellular processes, and genetic programs on cortical folding.Dual Perspectives Companion Paper: How Forces Fold the Cerebral Cortex, by Christopher D. Kroenke and Philip V. Bayly.

Keywords: OSVZ; Pax6; basal Radial Glia; ferret; neurogenesis; primate.

Figure 1.

Schematic drawings illustrating different types of developmental cerebral cortex folding. A, Bona fide, or true, cortical folding is characterized by the folding of the pial surface (thick purple line) and the underlying six neuronal layers (colored bands), whereas the ventricular surface of the white matter (wm; dashed line) remains smooth, as in the early pseudostratified neuroepithelium (left) from which it derives (Smart and McSherry, 1986; Bayer and Altman, 2005; Reillo et al., 2011). B, Pseudo, or false, cortical folding is typically characterized by the overgrowth of the early neuroepithelium (left) with minimal neurogenesis, and where both basal (solid line) and apical (ventricular, dashed line) surfaces are folded (Chenn and Walsh, 2002; Kingsbury et al., 2003).

Figure 2.

Schematic drawings illustrating the effect of bRGC abundance on cortical folding. A, Under physiological conditions, during development (left), there is a certain ration between the abundance of bRGCs (green) and apical Radial Glia Cells (aRGCs) (red) that leads to the relative tangential expansion of the neuronal layers, and this leads to cortical folding (Reillo et al., 2011). B, Reduced numbers of basal progenitors during development, particularly in OSVZ and especially bRGCs, lead to lower tangential expansion and thickening of neuronal layers, resulting in less folding (Reillo et al., 2011; Poluch and Juliano, 2015). C, Increased numbers of bRGCs during development produce an excessive tangential expansion of neuronal layers, and this leads to increased folding (Nonaka-Kinoshita et al., 2013; Stahl et al., 2013; Masuda et al., 2015; Florio et al., 2017).