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Mathematical modelling of cortical neurogenesis reveals that the founder population does not necessarily scale with neurogenic output

Picco, Noemi, García-Moreno, Fernando, Maini, Philip K., Woolley, Thomas and Molnár, Zoltán Mathematical modelling of cortical neurogenesis reveals that the founder population does not necessarily scale with neurogenic output. Cerebral Cortex 10.1101/206045
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Abstract

The mammalian cerebral neocortex has a unique structure, composed of layers of different neuron types, interconnected in a stereotyped fashion. While the overall developmental program seems to be conserved, there are divergent developmental factors generating cortical diversity amongst species. In terms of cortical neuronal numbers some of the determining factors are the size of the founder population, the duration of cortical neurogenesis, the proportion of different progenitor types, and the fine-tuned balance between self-renewing and differentiative divisions. We develop a mathematical model of neurogenesis that, accounting for these factors, aims at explaining the high diversity in neuronal numbers found across species. By framing our hypotheses in rigorous mathematical terms, we are able to identify paths of neurogenesis that match experimentally observed patterns in mouse, macaque and human. Additionally, we use our model to identify key parameters that would particularly benefit from accurate experimental investigation. We find that the timing of a switch in favor of symmetric neurogenic divisions produces the highest variation in cortical neuronal numbers. Surprisingly, assuming similar cell cycle lengths in primate 3 progenitors, the increase in cortical neuronal numbers does not reflect a larger size of founder population, a prediction that identified a specific need for experimental quantifications.

Item Type: Article
Status: In Press
Schools: Mathematics
Subjects: Q Science > QA Mathematics
Q Science > QP Physiology
Publisher: Oxford University Press
ISSN: 1047-3211
Funders: St John’s College Research Centre, National Science Foundation (grant number DMS1440386), MRC, Wellcome Trust, Royal Society, IKERBASQUE Research Fellowship
Date of First Compliant Deposit: 5 March 2018
Date of Acceptance: 1 March 2018
Last Modified: 27 Apr 2018 23:28
URI: http://orca.cf.ac.uk/id/eprint/109648

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