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Carol A. Mason, Ph.D.


E-mail: cam4@columbia.edu

Cell-cell interactions in the developing CNS

The aim of our research is to understand cellular and molecular mechanisms of axon guidance 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 serve to identify 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 corresponding receptors to those molecules in the retina, that direct divergent axon growth. The albino mutant, in which a point mutation in tyrosinase leads to decreased numbers of 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 dendritic spine and synapse formation, particularly the molecules regulating their development, and uses dynamic imaging to chronicle this process.

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

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

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

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

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

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

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