Mentor: Professor Karen Greif
Essential to the nervous system are chemicals called neurotransmitters, signals that mediate nerve cell communication. Nerve cells are connected by extensions called ‘processes’ that emanate from the cell body and allow for the propagation of these chemical signals. It is at the synapse, the terminal ending of a process and the interface between it and an adjoining process, that neurotransmitters are released and interpreted by the post-synaptic terminal of an adjoining nerve cell. Before this can occur, synaptic vesicles—neurotransmitter storehouses—must fuse with the plasma membrane and subsequently release their contents via a process termed exocytosis. This step is essential to neuronal communication, and therefore regulates the efficiency with which a chemically encoded message can be transmitted.
Synaptotagmins (syt) are a family of membrane fusion proteins that trigger the release of neurotransmitters; consequently their role in neuronal communication is vital. While this particular function of syt has been extensively detailed, little is known about its functional involvement in nerve cell outgrowth. The following observations have alluded to such roles in the developing nerve cell: syt expression is apparent in developing neurons several days prior to synapse formation; a positive correlation is observed between increased production of syt in neurons and process branching; and an upregulation of syt mRNA is apparent during the peak period of synaptogenesis. The question at hand is this: if syt functions only in neurotransmitter exocytosis, why should it be expressed substantially before any such events occur in the nerve cell? The sum of these observations may implicate syt in developmental growth events of the nerve cell—specifically, process outgrowth, extension, and branching.
This particular project seeks to understand the effect of syt on processes extension, retraction, and branching from the cell body. We will utilize a powerful gene-silencing technique called RNA interference. If effective, RNA interference should decrease the intracellular concentration of syt and allow for the assessment of the effects of syt depletion on forebrain neurons in stage-8 chicken embryos. Results from these tests, will elucidate insights regarding syts functional involvement in neurite outgrowth.