Area of Research
Axon Pathfinding & Synaptogenesis, Synapses & Circuits, Cell Specification & Differentiation
Axon pathfinding and circuit formation in the visual system and cerebellum.
The 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 microscopic approaches in vivo and in cell culture to dissect the molecular mechanisms development of neural circuits.
In our studies of axon guidance, we have analyzed the behaviors, cellular interactions and molecular directives of retinal axon growth cones during avoidance and crossing of the midline at the optic chiasm. This system is a model for axon navigation at the CNS midline, and for patterning the binocular projection. We have identified a molecular program of transcription factors and guidance receptors which regulates cell identity and projection of the ipsilateral retinal axon pathway through the optic chiasm. In our new work the aim is a threefold understanding of: the transcriptional regulation of guidance receptor expression; the activities of guidance receptors during interactions with specialized glia at the chiasm midline; and the mechanisms of crossing the midline. A genetic model for these studies is the albino, in which a lack of pigment in the eye leads to a reduced uncrossed projection and perturbations in vision.
To study how axonal growth cones interact with their synaptic target cells, we investigate the development of the cerebellum. In addition to various dynamic imaging approaches, these studies rely on purification and co-culture of selected cell types. We seek to identify both the cellular and molecular mechanisms of the steps in afferent mossy fiber growth and synapse formation with granule neuron targets, as well as the interactions between granule neuron axons and Purkinje cells that lead to dendrite and spine differentiation.
Manzini, M.C., Ward, M.S., Zhang, Q, Lieberman, M.D. and Mason, C.A.(2006)The stop signal revised: Immature cerebellar granule neurons intheexternal germinal layer arrest pontine mossy fiber growth. J.Neurosci. 26:6040-6051
Williams, S.E., Grumet ,M., Colman, D., Henkemeyer, M., Mason, C.A.,and Sakurai, T. (2006) A role for Nr-CAM in the patterning ofbinocular visual pathways. Neuron 50:535-47.
Herrera, E., Marcus, R., Li, S.,Williams, S.E., Erskine, L., Lai, E.,and Mason, C.A. (2004). Foxd1 isrequired for normal development of theoptic chiasm. Development 131:5727-39.
Heuer,H. and Mason, C.A. (2003) Thyroid hormone induces cerebellar Purkinjecell dendritic development via the thyroid hormone receptor alpha1. J.Neurosci. 19: 10604-10612.
Dunaevsky, A. and Mason, C.A. 2003 Spine motility with synaptic contact: A means toward an end? Trends Neurosci. 26: 155-160.
Williams, S.E., Mason, C.A., and Herrera, E. (2004) The optic chiasm as a midline choice point. Curr. Op. Neurobiol. 14: 51-60
Williams,S.E., Mann, F., Sakurai, T., Erskine, L.,Wei, A., Rossi, D.J., Gale,N., Holt, C.E., Mason, C.A., and Henkemeyer, M. (2003) Ephrin-B2 andEphB1 mediate retinal axon divergence at the optic chiasm. Neuron 39:919-935.
Herrera, E., Brown, L, Aruga, J., Rachel, R.A., Dolen, G., Mikoshiba,K., Brown, S. and Mason, C.A. (2003) Zic2 patterns binocular vision byspecifying the uncrossed retinal projection. Cell 114: 545-557.