Mentor: Dr. Karen Greif
Neuronal communication is dependent on established connections between nerve cells within the nervous system. Nerve cells are connected through ‘processes’ that radiate from the cell body and terminate at chemical synapses. At the synapse, chemical signals called neurotransmitters are packaged in synaptic vesicles and released into the synaptic cleft through exocytosis and bound by receptors on the post-synaptic neuron. This process, known as neurotransmission, is mediated by the release of Ca2+. Synaptotagmin, a prominent synaptic protein, directs the exocytosis of neurotransmitters through its function in calcium regulation.
Although the role of synaptotagmin (syt) in neuronal communication has been well studied, little is known about the role of synaptotamin in early neuronal development. Syt is believed to play a role in neurite outgrowth because of its early presence in nerve cells. Syt is found in nerve cells days before synaptogenesis, the formation of synapes, occurs. Researchers have also found that increasing levels of synaptotagmin in developing neurons increases the growth and branching of neuron processes. The exact role that synaptotagmin plays in neurite outgrowth is still undetermined, but observations, such as a Ca2+ requirement for process growth, may implicate synaptotagmin in process outgrowth and branching.
In order to determine what role synaptotagmin plays in neurite outgrowth; we will be investigating how changes in intracellular concentrations of synaptotagmin affect the development of neuron processes in stagte-8 chicken embryos. I will be concentrating specifically on how a decrease in synaptotagmin expression affects development. To achieve synaptotagmin knockdown, I will be utilizing RNA interference, a technique that silences syt gene expression through siRNA. Another secondary goal of the present study is to develop a reliable and efficient mode of siRNA delivery. This summer, I will be using liposome methodologies to knockdown syt.
This research is supported by grants from NIH and the Pennsylvania Health Research Formula Fund.