Professor, Anatomy & Neurobiology
School of Medicine

Cellular and Molecular Neurobiology 1. Role of extracellular matrix proteins in synaptogenesis 2. Factors affecting the regulation of gene expression in neurons and their targets

www.ucihs.uci.edu/anatomy/smith.html

The long term goal of my research is to understand the cellular interactions that control synaptic differentiation. At the neuromuscular junction, a protein called agrin triggers differentiation of the postsynaptic apparatus in the muscle fiber. To learn more about agrin's role in synapse formation we have focused on two questions. Does agrin serve a similar function in other regions of the nervous system and, what are the cellular mechanisms that regulate agrin gene expression? Consistent with agrin play ing a broad role in synaptogenesis, we find that the highest levels of agrin mRNA expression in developing chick ciliary ganglia coincide with the period when neurons first make synaptic contact with their target tissues in the eye. Using a single cell PCR technique, we have demonstrated that developmental changes in the pattern of alternatively spliced agrin mRNAs in the ganglion are a reflection of cell specific differences in agrin RNA splicing between neuronal and non-neuronal cells. Agrin is also expressed by many neuronal populations in the adult rat brain where the levels of expression can be altered by experimentally induced seizures. Since it is believed that the acquisition of new behaviors reflects activity dependent changes in neuronal circuitry, our observations suggest that agrin may play a role in this process. The effect of blocking agrin expression on different aspects of synapse formation are currently being tested.

Hilgenberg, L.G. and M.A. Smith, (2004) Agrin signaling in cortical neurons is mediated by a tyrosine kinase-dependent increase in intracellular Ca(2+) that engages both CaMKII and MAPK signal pathways. J. Neurobiol., 61: in press

Hoover, C.L., L.G.W. Hilgenberg, and M.A. Smith, (2003) The COOH-terminal domain of agrin signals via a synaptic receptor in CNS neurons. J. Cell Biol., 161:923-932.

Hilgenberg, L.G.W., et al., (2002) Agrin regulates neuronal responses to excitatory neurotransmitters in vitro and in vivo. Mol. Cell. Neurosci., 19:97-110.

Hilgenberg, L.G.W., C.L. Hoover and M.A. Smith. (1999) Evidence of an agrin receptor in cortical neurons. J. Neurosci., 19: 7384-7393.

Li, Z., L.G.W. Hilgenberg, D.K. O'Dowd and M.A. Smith. (1999) Formation of functional synaptic connections between cultured cortical neurons from agrin-deficient mice. J. Neurobiol., 39: 547-557.

Society for Neuroscience

Society for Developmental Biology

Interdepartmental Neuroscience Program

Link to this profile
https://faculty.uci.edu/profile/?facultyId=2392

Last updated
10/14/2004