In primates including human, the generation of neurons occurs during development while the brain is growing. This imposes natural constraints on adult brain repair. Recently it was discovered that unlike primates, adult birds continue to generate new neurons throughout their forebrain. These cells originate from discrete regions in the ventricular zone (VZ). The young neurons then adopt an elongated shape as they separate from the VZ at 20-30 um/hr using radial glial fibers as guides. Differentiation into mature neurons occurs 20-40 days later up to 6 mm away from their site of birth. The present proposal takes advantage of this model system for neurogenesis to study the origins of the new neurons. The PI's objectives are: 1) Identify the stem cells in the VZ of adult birds that give rise to the young migrating neurons. 2) Develop monoclonal antibodies (Mab) as markers to these precursor cells and to the young migrating neurons.3) Test the significance of radial glial proliferation in the adult avian brain.4) Understand the local movement of precursor cells within the VZ in relation to their proliferation dynamics. 5) Develops a new experimental approach to study neuronal migration. Electron microscopy (EM) and immunocytochemistry combined with [3H]-thymidine autoradiography will be used to identify the precursor cells in the VZ that give rise to neurons.Disaggregated VZ cells and transplantation and culture techniques are combined to study the early events leading to neurogenesis. The cells that give rise to the new neurons, their site of origin and their proliferation time table will be determined. The migration of live young neurons as they separate from the VZ will be followed under the microscope in brain slices.Their behavior on different terrains will reveal orientation cues used during migration. Cells born in the adult avian VZ only give rise to neurons. Neurogenesis occurs against a distinct background of unchanging adult brain parenchyma. Establishing the cellular prerequisites for adult neurogenesis and the mechanism that brings neurons to sites where needed in an adult brain could have a significant impact on approaches to brain repair.
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