Department of Biological Sciences
Stanford, CA 94305-5020
2005 Searle Scholar
We are interested in understanding the molecular mechanisms underlying the connection specificity between neurons at synapse formation level. In other words, how do neurons choose their synaptic partners during synaptogenesis? Can molecules encode target specificity?
Both anatomical and physiological evidences from different experimental systems support the notion that many synapses are selectively formed between specific synaptic partners at certain subcellular compartments (Gupta et al., 2000; Dantzker and Callaway, 2000; Kozloski et al., 2001). Cellular and subcellular target selection is essential for the functionality of neuronal circuits. These "hardwired" neuronal circuits are likely important for innate behaviors or forming the prototype neural substrate that can be further shaped by experience. It is not yet well understood if molecular mechanisms are the driving force of synaptic specificity and subcellular specificity. I propose to identify molecules that mediate the recognition between synaptic partners during synaptogenesis and to understand how recognition molecules direct synapse formation. In the last couple of years, we have analyzed synaptic specificity and synapse formation of a motor neuron, HSNL in C. elegans (Fig.1). We discovered that a pair of Immunoglobulin Superfamily proteins, SYG-1 and SYG-2, is essential for the synaptic choice of HSNL (Shen and Bargmann, 2003; Shen et al., 2004). In syg-1 or syg-2 mutants, presynaptic neuron HSNL contacts its normal synaptic partners but fails to form synaptic connections with them. Instead, ectopic synapses are formed onto abnormal postsynaptic targets. SYG-1 and SYG-2 both localize to synapses and bind to each other, acting as receptor and ligand. SYG-1 functions cell autonomously in the presynaptic neuron. SYG-2 functions in the guidepost cells, a group of epithelial cells that is essential for the correct formation of HSNL synapses (Shen and Bargmann, 2003; Shen et al., 2004). For the next few years, we will expand this discovery in several different directions:
Direction 1: How do SYG-1 and SYG-2 establish synaptic specificity and assemble synapses?
Direction 2: What are the other synaptic specificity molecules in C. elegans?
Direction 3: Are the vertebrate homologues of SYG-1 and SYG-2 involved in synaptogenesis ?
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