Carol A. Mason, Ph.D.

Research Summary
Cell-Cell Interactions in the Developing Brain

The primary aim of our research is to understand the mechanisms that underlie axon growth and the formation of specific synaptic connections. We use a battery of static and dynamic morphological approaches in intact brain and in tissue culture.

To study axon navigation through pathways, we examine the formation of bilateral projections in the mouse visual system. Our focus is the optic chiasm, a classic example of a "decision region" where fibers from each retina re-sort before traveling to targets on each side of the brain. By dye labeling axons, recording their morphology and behavior in real time, and using immunocytochemistry, we have observed that retinal axons diverge upon meeting a novel midline specialization composed of immature neurons and glia. In vitro and molecular approaches are being used to identify the cellular and molecular cues at this site that direct retinal axon divergence, and the mechanisms underlying specification of retinal ganglion cells to respond to these cues.

To study how axonal growth cones interact with their synaptic target cells, we investigate the early development of the mouse cerebellum in normal and mutant mice. In vivo studies have demonstrated the temporal coordination of axon ingrowth and contact with migrating or post-migratory targets. An in vitro model system, in which purified target granule neurons are co-cultured with selected afferent axons, has revealed that target cells regulate the growth of their afferents, providing a "stop-growing" signal for axon outgrowth prior to synapse formation. Based on evidence that afferent growth is modulated by neural activity, efforts are underway to further characterize the stop signal.

We have recently been able to purify Purkinje cells, allowing us to study the neural specificity of the stop-signal. In addition, this approach has demonstrated that granule cell afferents are a potent regulator of the differentiation of target Purkinje cells. To pursue the mechanisms of this interaction, we are testing the role of neurotrophins in Purkinje cell survival and differentiation, including the development of spines and synapses.

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

2. Baird, D.H., Trenkner, E., and Mason, C.A. (1996). Functional NMDA receptors are required for the arrest of axon growth by target neurons in vitro. J. Neurosci., 15: 2642-2648.

3. 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.

4. 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.

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

1. Growth and Guidance of Retinal Axons
The goal of this research is to provide information on the growth and guidance of axons within the central nervous system, using the formation of crossed and uncrossed projections of the retina in the mouse visual system as a model.This work should elucidate the signalling mechanisms used for axon navigation in this CNS pathway, a model for the patterning of bilateral projections, and provide a dynamic analysis of growth cone kinetics and interactions.
National Eye Institute
7/01/1999-6/30/2004

2. Vision Sciences Training Grant
National Eye Institute
9/30/2001-8/31/2006

Ad hoc member, NINDS, NEI Study Sections
Reviewing Editor: Journal of Neuroscience, Journal of Neurocytology
Editorial Board: Journal of Comparative Neurology, Faculty of 1000

axon, developmental neurobiology, growth cone, neuronal guidance, optic chiasma, cell cell interaction, interhemispheric transfer, retina, tissue /cell culture, visual pathway, cinemicrography, electron microscopy, histochemistry /cytochemistry, laboratory mouse