MOLECULAR MECHANISMS OF NEURAL STEM CELL LINEAGE PROGRESSION

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The concerted production of the correct number and diversity of neurons and glia is essential for intricate neural circuit assembly. In the developing cerebral cortex, radial glia progenitors (RGPs) are responsible for producing all neocortical neurons and certain glia lineages. We recently performed a quantitative clonal analysis by exploiting the unprecedented resolution of the genetic MADM (Mosaic Analysis with Double Markers) technology and discovered a high degree of non-stochasticity and thus deterministic mode of RGP behavior. However, the cellular and molecular mechanisms controlling the precise pre-programmed RGP lineage progression through proliferation, neurogenesis and gliogenesis remain unknown. To this end we use quantitative MADM-based experimental paradigms at single RGP resolution to define the sequential non-cell-autonomous and intrinsic cell-autonomous functions of candidate genes and signalling pathways controlling RGP-mediated cortical neuron and glia genesis and postnatal stem cell behavior.