New insights into the development of the human cerebral cortex

Zoltán Molnár*, Gavin J. Clowry, Nenad Šestan, Ayman Alzu'bi, Trygve Bakken, Robert F. Hevner, Petra S. Hüppi, Ivica Kostović, Pasko Rakic, E. S. Anton, David Edwards, Patricia Garcez, Anna Hoerder-Suabedissen, Arnold Kriegstein

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

170 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)432-451
Number of pages20
JournalJournal of Anatomy
Issue number3
Publication statusPublished - 2019


  • associative areas
  • calretinin
  • GABA
  • inhibitory interneurons
  • neurogenesis
  • neuroimaging
  • neuronal progenitors
  • prefrontal cortex
  • subplate neurons


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