BBS Faculty Member - Joshua Sanes

Joshua Sanes

Department of Molecular and Cellular Biology

Harvard University
335 Northwest Lab Building
52 Oxford St.
Cambridge, MA 02138
Tel: 617-496-8683
Fax: 617-495-0524
Lab Members: 12 postdoctoral fellows, 3 graduate students

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. Finally, in pursuit of these aims, we are engaged in generating novel transgenic strains that make it possible to visualize neurons and their connections in developing and adult animals, and in animal models of neurological and psychiatric disease.

Last Update: 8/22/2013


For a complete listing of publications click here.



Yamagata M, Sanes JR: Dscams and sidekicks direct lamina-specific synaptic connections in vertebrate retina. Nature, 2008; 451:465-469.

Kim IJ, Zhang Y, Yamagata M, Meister M and Sanes JR: Molecular identification of a novel retinal cell type that responds to upward motion. Nature, 2008; 452:478-482.

Williams AH, Valdez G, Moresi V, Qi X, McAnally J, Elliott JL, Bassel-Duby R, Sanes JR, Olson EN. MicroRNA-206 delays ALS progression and promotes regeneration of neuromuscular synapses in mice. Science. 2009; 326:1549-54.

Zipursky SL, Sanes JR. Chemoaffinity revisited: dscams, protocadherins, and neural circuit assembly. Cell. 2010; 143:343-53.

Kay JN, Voinescu PE, Chu MW, Sanes JR. Neurod6 expression defines new retinal amacrine cell subtypes and regulates their fate. Nat Neurosci. 2011; doi: 10.1038/nn.2859.

© 2013 by the President and Fellows of Harvard College