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Cerebral Cortex, Vol. 13, No. 6, 592-598, June 2003
© 2003 Oxford University Press

Cell Output, Cell Cycle Duration and Neuronal Specification: a Model of Integrated Mechanisms of the Neocortical Proliferative Process

V.S. Caviness, Jr1, T. Goto2, T. Tarui1, T. Takahashi1,2, P.G. Bhide1 and R.S. Nowakowski3

1 Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA, , 2 Department of Pediatrics, Keio University School of Medicine, Tokyo 160-8582, Japan and , 3 Department of Neuroscience and Cell Biology, UMDNJ–Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA

Address correspondence to R.S. Nowakowski, Department of Neuroscience and Cell Biology, UMDNJ–Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA. Email: rsn{at}umdnj.edu.

The neurons of the neocortex are generated over a 6 day neuronogenetic interval that comprises 11 cell cycles. During these 11 cell cycles, the length of cell cycle increases and the proportion of cells that exits (Q) versus re-enters (P) the cell cycle changes systematically. At the same time, the fate of the neurons produced at each of the 11 cell cycles appears to be specified at least in terms of their laminar destination. As a first step towards determining the causal interrelationships of the proliferative process with the process of laminar specification, we present a two-pronged approach. This consists of (i) a mathematical model that integrates the output of the proliferative process with the laminar fate of the output and predicts the effects of induced changes in Q and P during the neuronogenetic interval on the developing and mature cortex and (ii) an experimental system that allows the manipulation of Q and P in vivo. Here we show that the predictions of the model and the results of the experiments agree. The results indicate that events affecting the output of the proliferative population affect both the number of neurons produced and their specification with regard to their laminar fate.


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