The long-term goal of this research is to understand from a cell biological perspective how neurons establish distinct axonal and dendritic domains that differ in form and function. This feature of nerve cells is inextricably linked to their normal function-- the geometry of axons and dendrites, the distributions of channels in the neuronal membrane, the localization of synaptic terminals over its surface, give a neuron its identity. Alterations in neuronal polarity contribute to the pathophysiology of many neural disorders and may underlie the etiology of some neurologic diseases. The development of neuronal polarity will be studied in cell cultures of neurons dissociated from the embryonic rat hippocampus. Key stages in the development of polarity will be analyzed by high resolution time-lapse video recording in conjunction with electron microscopy. Cellular structures and processes important to polarization will also be studied. These include the Golgi apparatus and microtubule-organizing centers, the sorting of membranous organelles to axons and dendrites, and the supply of materials needed for growth from the soma to elongating processes. To determine when polarization becomes irreversibly specified, the response of cells to transection of their axons at successive stages of development will be assessed. Finally, the contact-induced branching of dendrites will be investigated, focusing on the signal for branching and the dendritic response that results in the formation of a branch.
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