Research:
Information processing in the brain occurs at synapses, and defects in synapse formation are likely to underlie many neurological and psychiatric diseases. We are therefore interested in the molecules and structures that regulate synapse formation. For studies of synaptic differentiation, we have used the skeletal neuromuscular junction, because it is the best studied of all synapses and therefore a good subject for molecular analysis. Our major aim has been to identify components that mediate intercellular interactions between pre- and postsynaptic cells. To learn which components are the functionally critical ones, we combine studies of dissociated cells in vitro with molecular genetic analysis of knockout mice in vivo. We are currently extending our studies from early developmental events to maturation, maintenance and even aging of the synapse.. To learn how neurons recognize appropriate partners and assemble into circuits, we have chosen the retinotectal projection. We have initiated studies of how retinal cells receive and make synapses in specific laminae of the eye and brain, respectively. Such laminar restrictions are major determinants of specific connectivity in many parts of the brain, including the cerebral cortex. In collaboration with Markus Meister, we are correlating molecular and histological features of retinal cell types with with their functional properties. A final set of studies, done in collaboration with Jeff Lichtman, aims to devise novel transgenic methods for visualizing synapse formation and synaptic circuits in live animals over time. By using these methods we are learning how the molecules identified in the first two projects actually exert their cellular effects.
Selected Publications: Umemori H, Linhoff MW, Ornitz DM, and Sanes JR : (2004) FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain. Cell 2004; 118 :257-270 Nishimune H, Sanes JR , Carlson SS: (2004) A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals. Nature 2004; 432:580-587 Kishi M*, Pan YA*, Crump JG, Sanes JR : (2005) Mammalian SAD kinases are required for polarization of forebrain neurons. Science ; 307 :929-932. Fox, M., Sanes JR , et al. (2007) Distinct target-derived signals organize formation, maturation and maintenance of motor nerve terminals. Cell; 129:179-193 Livet J, Weissman TA, Kang H, Draft RW, Lu J, Bennis RA, Sanes JR , Lichtman JW. (2007) Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system. Nature. 450:56-62. Kim IJ, Zhang Y, Yamagata M, Meister M, Sanes JR . (2008) Molecular identification of a retinal cell type that responds to upward motion. Nature 452:478-82. Yamagata M, Sanes JR . (2008) Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina. Nature 451:465-9.
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