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31.03.16 Evolutionary progression in development of cortex modelled in vitro

last modified Apr 06, 2016 03:46 PM
The Livesey lab publish new results on modelling cortical development in vitro in 2D and 3D to explore mechanisms that control final size of the cortex in primates
31.03.16 Evolutionary progression in development of cortex modelled in vitro

Graphical abstract from the paper

2D and 3D Stem Cell Models of Primate Cortical Development Identify Species-Specific Differences in Progenitor Behavior Contributing to Brain Size

Tomoki Otani, Maria C. Marchetto, Fred H. Gage, Benjamin D. Simons and Frederick J. Livesey (2016) Cell Stem Cell (In Press Corrected Proof published online 31 March 2016)

doi: 10.1016/j.stem.2016.03.003


 Highlights and summary from the paper: 

  • Human and primate pluripotent stem cells (PSCs) can replicate cortical development in culture
  • PSC-derived cortical progenitors from different species expand to different degrees
  • Clonal analysis reveals marked difference in neurogenesis output over time
  • Species-specific timing differences in neurogenesis are regulated cell autonomously 


Variation in cerebral cortex size and complexity is thought to contribute to differences in cognitive ability between humans and other animals. Here we compare cortical progenitor cell output in humans and three nonhuman primates using directed differentiation of pluripotent stem cells (PSCs) in adherent two-dimensional (2D) and organoid three-dimensional (3D) culture systems.

Clonal lineage analysis showed that primate cortical progenitors proliferate for a protracted period of time, during which they generate early-born neurons, in contrast to rodents, where this expansion phase largely ceases before neurogenesis begins.

The extent of this additional cortical progenitor expansion differs among primates, leading to differences in the number of neurons generated by each progenitor cell. We found that this mechanism for controlling cortical size is regulated cell autonomously in culture, suggesting that primate cerebral cortex size is regulated at least in part at the level of individual cortical progenitor cell clonal output.



Reproduced under Creative Commons License (CC BY 4.0).

Studying development to understand disease

The Gurdon Institute is funded by the Wellcome Trust and Cancer Research UK to study the biology of development, and how normal growth and maintenance go wrong in cancer and other diseases.