Cerebral Cortex Advance Access originally published online on January 4, 2007
Cerebral Cortex 2007 17(10):2433-2442; doi:10.1093/cercor/bhl151
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Computational Models of Neocortical Neuronogenesis and Programmed Cell Death in the Developing Mouse, Monkey, and Human
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA, 1 Current address: Environmental Systems Biology Group, Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, RTP, NC 27709, USA
Address correspondence to Elaine M. Faustman, University of Washington, Institute for Risk Analysis and Risk Communication, Department of Environmental and Occupational Health Sciences 4225 Roosevelt Way NE, Suite #100, Seattle, WA 98105-6099, USA. Email: faustman{at}u.washington.edu.
This paper presents a computational model allowing quantitative simulations of acquisition of neocortical neuronal number across mammalian species. When extrapolating scientific findings from rodents to humans, it is particularly pertinent to acknowledge the importance of the accelerated enlargement of the neocortex during human evolution. Neocortex development is marked by discrete stages of neural progenitor cell proliferation and death, neuronal differentiation, and neuronal programmed cell death. We have developed computational models of human and rhesus monkey neocortical neuronal cell acquisition based on experimentally derived parameters of cell cycle length, commitment to cell cycle exit, and cell death. Our model results agree with independent stereological studies estimating neocortical neuron number in adult and developing rhesus monkey and human. Comparisons of our primate models with previously developed rodent models suggest correlations between the lengthening of the duration of the neuronogenesis period and a lengthening of the cellular processes of cell cycle progression and death can account for the vast increase in size of the primate neocortex. Furthermore, when compared with rodents, we predict that cell death may play a larger role in shaping the primate neocortex. Our mathematical models of the development and evolution of the neocortex provide a quantitative, biologically based construct for extrapolation between rodent and humans. These models can assist in focusing future experimental research on the differing mechanisms of rodent versus human neocortical development.
Key Words: apoptosis • cell cycle • evolution • mathematical model • neuron number • rhesus