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Dr. Joshua Sanes

Professor Molecular & Cellular Biology

Harvard University
MCB, Fairchild Bldg., Rm. 143
7 Divinity Ave.
Cambridge, MA 02138
Phone: 617-496-8683
Fax: 617-496-9590
Email: sanesj@mcb.harvard.edu
Predocs: 4 Postdocs: 10 Completed PhD's: 10

 Joshua Sanes

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 many 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 that transduce these signals. 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.

A second project extends this analysis to the vertebrate central nervous system, with an emphasis the issues of specificity. We have chosen the retinotectal projection because of its relative accessibility, and initiated studies of how retinal axons receive and make synapses 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 from the neuromuscular junction to synapses of the brain.

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.

 

References:

  • 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

  • Nishimune H, Sanes JR, Carlson SS: A synaptic laminin-calcium channel interaction organizes active zones in motor nerve terminals. Nature 2004; 432:580-587

  • Kishi M*, Pan YA*, Crump JG, SanesJR: Mammalian SAD kinases are required for polarization of forebrain neurons. Science 2005; 307:929-932.

  • Fox, M., Sanes, JR, et al. Distinct target-derived signals organize formation, maturation and maintenance of motor nerve terminals. Cell 2007; 129:179-193