What Are the Human-Specific Aspects of Neocortex Development?

Abstract

When considering what makes us human, the development of the neocortex, the seat of our higher cognitive abilities, is of central importance. Throughout this complex developmental process, neocortical stem and progenitor cells (NSPCs) exert a priming role in determining neocortical tissue fate, through a series of cellular and molecular events. In this Perspective article, we address five questions of relevance for potentially human-specific aspects of NSPCs, (i) Are there human-specific NSPC subtypes? (ii) What is the functional significance of the known temporal differences in NSPC dynamics between human and other great apes? (iii) Are there functional interactions between the human-specific genes preferentially expressed in NSPCs? (iv) Do humans amplify certain metabolic pathways for NSPC proliferation? and finally (v) Have differences evolved during human evolution, notably between modern humans and Neandertals, that affect the performance of key genes operating in NSPCs? We discuss potential implications inherent to these questions, and suggest experimental approaches on how to answer them, hoping to provide incentives to further understand key issues of human cortical development.

Laminar dynamics of deep projection neurons and mode of subplate formation are hallmarks of histogenetic subdivisions of the human cingulate cortex before onset of arealization

“…SVZ prominence is an additional excellent indicator of the mesocortical cingulate thickness, which diminishes towards the limbus, parallel with the CC development. Thus, our study further supports the general concept of the SVZ importance for primate cortex formation (Rakic and Nowakowski 1981 ; Haubensak et al 2004 ; Hevner 2007 ; Kelava et al 2012 ; Dehay et al 2015 ; Popovitchenko and Rasin 2017 ; Mora-Bermúdez and Huttner 2022 ). The fact that the primate characteristic SVZ is producing DPN—predominantly of pyramidal type, shows the tremendous importance of pyramidal neurons for the basic cortical architecture establishment in humans (Cajal 1911 ; Marin-Padilla 1983 ; Haydar et al 2000 ).…”

Pan-cancer surveys indicate cell cycle-related roles of primate-specific genes in tumors and embryonic cerebrum

“…Such a process has been phrased as "a small step for the cell, a giant leap for mankind" [98]. A few case studies have shown consistent results, reporting that regulatory evolution contributed to a longer and faster proliferation phase of human NECs [100][101][102][103][104]. A modified version of the radial unit hypothesis emphasizes the increase in a derived stem cell population called outer or basal radial glial cells (oRGs or bRGs) in the fetal stage [105][106][107][108][109], when an excess of PSGs are expressed (Fig.…”

Neocortical neurogenesis in development and evolution—Human‐specific features

“…The combination of the six amino acid substitutions in these three proteins in modern humans appears to be unique. Therefore, this likely modern human‐specific set of six amino acids became a prime candidate to potentially explain the differences in AP metaphase duration and AP chromosome segregation fidelity observed between modern humans and chimpanzees, and potentially many other species, including Neanderthals (Mora‐Bermúdez & Huttner, 2022; Mora‐Bermúdez et al., 2016; Mora‐Bermúdez et al., 2022). Interestingly from an evolutionary point of view, and conveniently from an experimental point of view, all six ancestral amino acids are found not only in Neanderthals and Denisovans, but also in chimpanzees and other great apes, as well as many other species, including other primates, cetaceans, and, notably, rodents.…”