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 most of our studies, we have used the skeletal neuromuscular junction, because it is the best studied of all synapses and therefore a good subject for molecular analysis of developmental processes. Our major aim has been to identify components that mediate intercellular interactions: molecules that muscle cells use to trigger presynaptic differentiation of axons, molecules that axons use to organize postsynaptic differentiation of muscle, and receptors than transduce these signals. To learn which of the proteins we find are the functionally critical ones, we combine studies of dissociated nerve and muscle cells in vitro with molecular genetic analysis of knockout mice in vivo. A second project extends this analysis to the vertebrate central nervous system. We have chosen the retinotectal projection because of its relative accessibility, and initiated studies of how retinal axons arborize and synapse in specific laminae. Such laminar restrictions are major determinants of specific connectivity in many parts of the brain, including the cerebral cortex. Our hope is to apply insights and reagents obtained from the neuromuscular junction to the more complicated, but perhaps even more interesting, synapses of the brain.
Selected Publications: Yamagata M, Weiner JA, Sanes JR: Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina. Cell, 2002; 110:649-660. Misgeld T, Burgess RW, Lewis RM, Cunningham JM, Lichtman JW and Sanes JR: Roles of neurotransmitter in synapse formation: development of neuromuscular junctions lacking choline acetyltransferase. Neuron, 2002; 36:635-648. Wang X, Weiner JA, Levi S, Tovar KR, Craig AM, Bradley A, Sanes JR: Gamma protocadherins are required for survival of spinal interneurons. Neuron, 2002; 36:843-854. Buffelli M, Burgess RW, Feng G, Lobe C, Lichtman JW, and Sanes JR: Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition. Nature 2003; 424: 430-434. Umemori H, Linhoff MW, Ornitz DM, and Sanes JR: FGF22 and its close relatives are presynaptic organizing molecules in the mammalian brain. Cell 2004; 118:257-270.
|
