The research in my lab seeks to gain insight into the cellular and molecular mechanisms regulating cell proliferation, determination, migration and differentiation during the development of the mammalian forebrain, and in particular two highly organized, phenotypically diverse and laminated structures: the cerebral cortex and olfactory bulb. We are focusing our efforts on the pattern of cell proliferation and migration of a discrete population of neuronal progenitor cells and the progeny to which they give rise.
The neuronal progenitor cells are situated in a region of the brain surrounding the anterior part of the lateral ventricle, referred to as the SVZa. We have shown that SVZa-derived cells, which stain with neuron-specific markers, migrate exceptionally long distances, exceeding that of any other neurons in the CNS, along a well-circumscribed pathway. We are analyzing the mode(s) of cell migration of SVZa-derived neurons using retroviral mediated gene transfer to track the cells, and the putative biochemical markers involved in the guidance of SVZa derived cells using immunohistochemical techniques. SVZa-derived neurons are especially interesting because, unlike all other neurons in the CNS, the SVZa-derived neurons divide as they migrate.
We are also developing a way to use time-lapse video recordings to track the behavior of SVZa-derived neurons in order to study the dynamic changes in their morphology as they migrate and to study how the process of cell division is orchestrated by migrating neurons. To examine the regulation of the phenotypic properites of the neuronal progenitor cells and that of their descendants, we are examining them in vitro and following transplantation. Our analysis will provide clues to factors guiding the directed migration of neurons what governs the proliferation and differentiation neurons.