RESEARCH INTERESTS
The formation of specific synaptic connections between neurons is critical for the development, regeneration and plasticity of the nervous system, and our interest is in understanding the molecular basis of this process. Our aim is to identify the signals that direct synapse formation in the mammalian nervous system and to understand how these signals induce the specialized pre- and post-synaptic structures of the synapse. Much of our work focuses on a synaptogenic factor called agrin, which plays an essential role in neuromuscular synapse formation and is also expressed elsewhere in the developing peripheral and central nervous systems. This work is in two main areas: (1) First, we are investigating agrin's role at the developing neuromuscular synapse and in particular, how it acts to localize the transmitter receptor in the postsynaptic membrane. (2) Second, we are investigating agrin's role in the formation of other neuronal synapses in the peripheral and central nervous systems. We are addressing these questions both in culture systems and animal models (knockout mice), using a combination of cellular, molecular, and biochemical techniques.
SELECTED PUBLICATIONS
Ferns, M.J., Campanelli, J.T., Hoch, W., Scheller, R.H., & Hall, Z. (1993) The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycans. Neuron 11(3): 491-502.
Ferns, M., Deiner, M., & Hall, Z. (1996) Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation. J. Cell Biol. 132(5): 937-944.
Borges, L., & Ferns, M. (2001) Agrin-induced phosphorylation of the acetylcholine receptor regulates cytoskeletal anchoring and clustering. J. Cell Biol. 153:1-11.
Ferns, M., & Carbonetto, S. (2001) Challenging the neurocentric view of neuromuscular synapse formation.Neuron 30(2):311-314.
Gingras, J., Rassadi, S., Cooper, E., & Ferns, M.(2002) Agrin plays an organizing role in the formation of sympathetic synapses. J. Cell Biol. 158(6):1109-1118.
Gingras, J., Spicer, J., Altares, M., Zhu, Q., Kuchel, G.A. and Ferns, M. (2005) Agrin becomes concentrated at neuroeffector junctions in developing rodent urinary bladder.Cell & Tissue Research, 320: 115-125.
Gingras, J., Rassadi, S., Cooper, E., and Ferns, M.(2006) Synaptic transmission is impaired at neuronal autonomic synapses in agrin null mice. J. Neurobiol., in press.
