Neurons and glia in the developing brain arise from pluripotent neuroepithelial progenitor cells (NE cells). These pluripotent NE cells grow rapidly after being excised from the presumptive cortex of E14 rat embryos and placed into culture. When exposed even briefly to platelet- derived growth factor (PDGF), the NE cells enter a state of growth arrest and differentiate into neurons. The broad objective of my project is to define the molecular basis of PDGF-induced growth arrest. I reason that lesions in the mechanism whereby PDGF induces growth arrest in these neural progenitor cells may give rise to primary tumors of the central nervous system. My work will focus on the role of G1 phase cyclin associated CDKs(Cyclin-Dependent Kinase) in control of NE cell proliferation and neuronal differentiation. Using immunoblotting procedures, I will monitor the abundance level of cyclins and CDK inhibitors in PDGF-treated NE cell cultures. To define the relationship between PDGF-induced growth arrest and neuronal differentiation, I will use adenoviral and retroviral expression vectors, to manipulate CDK activity in NE cells at a point downstream of PDGF receptor activation. In this way, I can determine if growth arrest is necessary and/or sufficient for neuron formation.
