My laboratory is engaged in research to understand the cellular and molecular mechanisms regulating the proliferation, migration and differentiation of neurons during the development of the mammalian forebrain. The neurons destined for the forebrain arise from the germinal ventricular and subventricular zones surrounding the lateral ventricles, although the postnatal subventricular zone generates predominantly glia. Studies in my laboratory, however, have demonstrated that cells originating from a discrete region of the anterior part of the neonatal subventricular zone (referred to as the SVZa) are destined exclusively for the olfactory bulb, where they differentiate into one of two types of interneurons. They either become GABAergic granule cells of the granule cell layer or periglomerular cells of the glomerular layer. Our ongoing experiments are directed at determining the guidance mechanisms used by migrating SVZa-derived neurons. We are examining whether, following transplantation, newly generated, nonSVZa-derived neurons, that usually migrate along radial glial fibers, can decipher the cues read by the SVZa-derived cells. Conversely we are examining whether SVZa-derived cells have the ability to advance along glial fibers when transplanted. These experiments will help elucidate the mechanisms underlying the directed migration of neurons in the developing CNS. We are pursuing other transplantation experiments to determine whether SVZa cells can substitute for the loss of neurons that occurs in Parkinson’s disease or Huntington’s disease. In conjunction with the transplantation experiments, we have been isolating and characterizing SVZa progenitor cells in vitro and have demonstrated that practically all of them express neuron-specific markers and divide in culture. We are currently analyzing the proliferative behavior and neurotransmitters phenotype of SVZa cells in vitro in response to neurotrophic factors. Additional efforts are directed at determining the distribution and identity of candidate cell surface and extracellular matrix molecules which may govern the directed migration of the SVZa-derived cells and prevent them from leaving the pathway.