New insights into the development of the human cerebral cortex

Abstract

The cerebral cortex constitutes more than half the volume of the human brain and is presumed to be responsible for the neuronal computations underlying complex phenomena, such as perception, thought, language, attention, episodic memory and voluntary movement. Rodent models are extremely valuable for the investigation of brain development, but cannot provide insight into aspects that are unique or highly derived in humans. Many human psychiatric and neurological conditions have developmental origins but cannot be studied adequately in animal models. The human cerebral cortex has some unique genetic, molecular, cellular and anatomical features, which need to be further explored. The Anatomical Society devoted its summer meeting to the topic of Human Brain Development in June 2018 to tackle these important issues. The meeting was organized by Gavin Clowry (Newcastle University) and Zoltán Molnár (University of Oxford), and held at St John's College, Oxford. The participants provided a broad overview of the structure of the human brain in the context of scaling relationships across the brains of mammals, conserved principles and recent changes in the human lineage. Speakers considered how neuronal progenitors diversified in human to generate an increasing variety of cortical neurons. The formation of the earliest cortical circuits of the earliest generated neurons in the subplate was discussed together with their involvement in neurodevelopmental pathologies. Gene expression networks and susceptibility genes associated to neurodevelopmental diseases were discussed and compared with the networks that can be identified in organoids developed from induced pluripotent stem cells that recapitulate some aspects of in vivo development. New views were discussed on the specification of glutamatergic pyramidal and γ‐aminobutyric acid (GABA)ergic interneurons. With the advancement of various in vivo imaging methods, the histopathological observations can be now linked to in vivo normal conditions and to various diseases. Our review gives a general evaluation of the exciting new developments in these areas. The human cortex has a much enlarged association cortex with greater interconnectivity of cortical areas with each other and with an expanded thalamus. The human cortex has relative enlargement of the upper layers, enhanced diversity and function of inhibitory interneurons and a highly expanded transient subplate layer during development. Here we highlight recent studies that address how these differences emerge during development focusing on diverse facets of our evolution.

Robust Production of Uniform Human Cerebral Organoids from Pluripotent Stem Cells

“…These studies further revealed that in older hCOs, while markers of RG cells and mature neurons were maintained, the cells expressing the markers became intermingled, and the organized layering of ventricular units evident in earlier hCOs was lost, as reported previously (Watanabe, Buth et al, 2017). Altogether, this analysis demonstrates that the hCOs generated using the optimized pipeline display organization and patterning reminiscent of that observed in vivo (Molnar, Clowry et al, 2019).…”

Cortical responses to tactile stimuli in preterm infants

“…Subplate neuronal networks provide hence a relay between thalamus and cortex, and the subplate neurons allow coordination of cortical network ensembles, which is believed to provide key guidance for early cortical organization (Luhmann et al, ). Our time–frequency analysis indicated differential development of higher‐ and lower‐frequency oscillations at around the time when the main invasion of thalamo‐cortical innervation is known to take place in the human (Kostovic & Judas, ; Molnar et al, ). It is easy to envision that the observed changes, a developmental decline in higher frequency and an increase in lower frequency, may reflect the changing subplate‐cortex interaction (Kostovic & Judas, ) which is well characterized in the rodent models (Luhmann & Khazipov, ).…”

Emerging Roles of Long Non-Coding RNAs as Drivers of Brain Evolution

“…The substantial increase in human brain size is mainly due to the tremendous expansion of the neocortex, characterized by new cortical areas, and a strong increase in connectivity [106]. In humans, the neocortex constitutes more than a half of the volume of the human [107], and a 10-fold rise in human cortical areas is estimated compared to early mammals [108]. Higher order associative cortical areas have tremendously been enlarged in the human cortex [109,110].…”

“…Another hallmark of human brain evolution is a highly enlarged subplate layer emerging during development, where earliest cortical circuits are established from the firstly generated neurons [107].…”