Mathematical modeling supports substantial mouse neural progenitor cell death.
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.


CONCLUSIONS
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.
McConnell
Michael J
MJ
Crick-Jacobs Center for Theoretical and Computational Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. mikemc@salk.edu
MacMillan
Hugh R
HR
Chun
Jerold
J
D000818:Animals; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D003198:Computer Simulation; D004622:Embryo, Mammalian; D051379:Mice; D008959:Models, Neurological; D009474:Neurons / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*