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Open Access Research article

Mathematical modeling supports substantial mouse neural progenitor cell death

Michael J McConnell12*, Hugh R MacMillan3 and Jerold Chun2*

Author Affiliations

1 Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA

2 Helen L Dorris Neuropsychiatric Disorder Institute and Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA

3 Department of Mathematical Sciences, Clemson University, Clemson, SC 29634, USA

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Neural Development 2009, 4:28  doi:10.1186/1749-8104-4-28

Published: 14 July 2009

Abstract

Background

Existing quantitative models of mouse cerebral cortical development are not fully constrained by experimental data.

Results

Here, we use simple difference equations to model neural progenitor cell fate decisions, incorporating intermediate progenitor cells and initially low rates of neural progenitor cell death. Also, we conduct a sensitivity analysis to investigate possible uncertainty in the fraction of cells that divide, differentiate, and die at each cell cycle.

Conclusion

We demonstrate that uniformly low-level neural progenitor cell death, as concluded in previous models, is incompatible with normal mouse cortical development. Levels of neural progenitor cell death up to and exceeding 50% are compatible with normal cortical development and may operate to prevent forebrain overgrowth as observed following cell death attenuation, as occurs in caspase 3-null mutant mice.