Control of cerebral size and thickness

Abstract

The mammalian neocortex is a sheet of cells covering the cerebrum that provides the structural basis for the perception of sensory inputs, motor output responses, cognitive function, and mental capacity of primates. Recent discoveries promote the concept that increased cortical surface size and thickness in phylogenetically advanced species is a result of an increased generation of neurons, a process that underlies higher cognitive and intellectual performance in higher primates and humans. Here, we review some of the advances in the field, focusing on the diversity of neocortical progenitors in different species and the cellular mechanisms of neurogenesis. We discuss recent views on intrinsic and extrinsic molecular determinants, including the role of epigenetic chromatin modifiers and microRNA, in the control of neuronal output in developing cortex and in the establishment of normal cortical architecture.

Modern human changes in regulatory regions implicated in cortical development

“…The regulatory regions reported here significantly overlap with putative modern human positively-selected regions and schizophrenia genomic loci, and control a set of genes among which we find a high number related to chromatin regulation, and most specifically the SETD1A/HMT complex. Regulators of chromatin dynamics are known to play key roles during cell-fate decisions through the control of specific transcriptional programs [41][42][43]. Both SETD1A and ASH2L, core components of the HMT complex, regulate WNT/β-CATENIN signaling [38][39][40]44], which influences cellfate decisions by promoting either self-maintenance or differentiation depending on the stage of progenitor differentiation ( Fig.…”

The Cell Biology of Neurogenesis: Toward an Understanding of the Development and Evolution of the Neocortex

“…Concerning events within the nucleus, notably transcriptional regulation and epigenetics, and regulation by microRNAs, we refer the reader to recent reviews (Cremisi 2013, Hirabayashi & Gotoh 2010, Tuoc et al 2014. With regard to cell biological mechanisms, we do not describe the role of transmembrane and cytoplasmic proteins in this section, as these are addressed, at least in part, in other sections.…”

“…We discuss the basic principles of cortical neurogenesis and their cell biological basis www.annualreviews.org • Cell Biology of Neurogenesis and then proceed to the stem and progenitor cell diversity involved in expanding the neocortex. Topics beyond the scope of this review include transcriptional regulation of neurogenesis in the developing neocortex, adult neurogenesis, neuronal migration and differentiation, and gliogenesis; here, the reader is referred to recent reviews (Cremisi 2013, Guerout et al 2014, Hippenmeyer 2014, Ninkovic & Götz 2013, Paridaen & Huttner 2014, Rowitch & Kriegstein 2010, Tuoc et al 2014.…”

Modern human changes in regulatory regions implicated in cortical development

“…The regulatory regions reported here significantly overlap with putative modern human positively-selected regions and schizophrenia genomic loci, and control a set of genes among which we find a high number related to chromatin regulation, and most specifically the SETD1A/HMT complex. Regulators of chromatin dynamics are known to play key roles during cell-fate decisions through the control of specific transcriptional programs [36–38]. Both SETD1A and ASH2L, core components of the HMT complex, regulate WNT/ β -CATENIN signaling [28–30, 39], which influences cell-fate decisions by promoting either self-maintenance or differentiation depending on the stage of progenitor differentiation (Figure 3).…”