P46. Generation of transgenic mice for the inducible expansion of neural stem cells

Abstract

During development of the mammalian brain, neurons are generated from divisions of neural stem cells. The embryonic neocortex contains two main types of neural precursors, apical progenitors (APs) and more lineage committed basal progenitors (BPs), whose expansion is believed to contribute to an increase in cortical thickness and cortical surface area, respectively, during development and evolution of the mammalian brain. The length of the cell cycle is known to influence the switch from proliferative to neuron-generating divisions of neural stem and progenitor cells. Specifically, G1 phase was shown to lengthen during neuron-generating divisions and a shortening of G1 by overexpression of the cdk4/cyclinD1 complex was shown to promote the expansion of BPs. These observations suggest that an increase in cortical surface area and, in principle, generation of mice with gyrencephalic brains, could be achieved by controlling the expression of cdk/cyclin complexes during cortical development. Therefore, we generated transgenic mouse lines for the tissue-specific, inducible, and temporally controlled overexpression of cdks/cyclins in neural precursors and investigated the effect of these manipulations on brain development, cytoarchitecture and size. Our data may provide important information on stem cell contribution to tissue formation and a better understanding of the cellular mechanisms triggering the increase in cortical surface area observed during evolution of the mammalian brain.