Carol A. Mason, PhD

The aim of our research is to understand the cellular interactions among neurons and between neurons and glia during axonal outgrowth and formation of synaptic connections in mammalian (rodent) brain. Our studies rely on a battery of approaches, combining dye-labeling of individual nerve cells, correlated light and electron microscopy, immunohistochemistry, in situ hybridization, and video time-lapse studies of cellular behavior in intact tissue and in culture. These methods provide approaches for identifying molecular factors mediating axon guidance and synapse formation.

Studies on axon guidance in the visual system aim to unravel molecular mechanisms of pathfinding in the optic chiasm, a "choice point" where growth cones navigate to the same or opposite side of the brain. Novel neuronal and glial cellular specializations in the midline are candidate cues for axon divergence. Current work aims to characterize molecules expressed by these cells, and the corresponding receptors to those molecules in the retina, that direct divergent growth. The albino mutant, in which a point mutation in tyrosinase leads to a decrease in uncrossed retinal axons, offers a genetic model to address these issues.

The cerebellum is a model for axon-target cell interactions, both the signals that regulate presynaptic axon growth and those that direct target cell development. In vitro studies based on defined cell populations allow the direct examination of growth cone behavior, and serve as assays for the molecules underlying axon growth and selection of synaptic partners. We are investigating the molecular basis of the "stop-growing" signal on target granule cells, and the factors released by presynaptic axons that stimulate target Purkinje cell differentiation and formation of synaptic contacts. New work examines the dynamics of spine formation and motility, and the afferent interactions instigating these behaviors, which will serve as an additional assay for factors regulating these processes during synaptogenesis and plasticity.

Selected Publications:

• Baptista, C.A., Blazeski, R., Hatten, ME, and Mason, C.A. Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro. Neuron 12: 243-260 (1994).

• Baird, D. H., Trenkner, E., and Mason, C.A. Functional NMDA receptors are required for the arrest of axon growth by target neurons in vitro. J. Neuroscience. 16: 2642-2648 (1996).

• Marcus, R.C., Wang, L.-C., and Mason, C.A. Retinal axon divergence in the optic chiasm: Midline cells are unaffected by the albino mutation. Development 122: 859-868 (1996).

• Wang, L.-C., Rachel, R.A., Marcus, R.C., and Mason, C.A. Retinal axon pathfinding: Diffusible cues from the chiasm and the floor plate suppress growth of all retinal axons. Neuron 17: 849-862 (1996).

• Mason, C.A., and Wang, L.-C. Growth cone form is behavior-specific and, consequently, position-specific. J. Neurosci. 17: 1086-1100 (1997).

• Mason, C.A., and Sretavan, D.W. Glia, neurons, and axon pathfinding during optic chiasm development. Curr. Op. Neurobiol. 7: 647-653 (1997).

• Zhang, Q., and Mason, C.A. Developmental regulation of mossy fiber afferent interactions with target granule cells. Devel. Biol. 195: 75-87 (1998).

• Morrison, M.E. and Mason, C.A. Granule neuron regulation of Purkinje cell development: Striking a balance between neurotrophin and glutamate signaling. J. Neurosci. 18: 3563-3573 (1998).

• Shimada, A., Mason, C.A., and Morrison, M.E. TrkB signaling modulates spine density and morphology independent of dendrite structure in cultured neonatal Purkinje cells. J. Neurosci. 18: 8559-8571 (1998).

• Marcus, R.C., Shimamura, K., Sretavan, D., Lai, E., Rubenstein, J.L.R., and Mason, C.A. Domains of regulatory genes and the developing optic chiasm: correspondence with retinal axon paths and candidate signaling cells. J. Comp. Neurol. 403: 346-359 (1999).