Cell-cell Interactions in the developing visual system
Our research program seeks to understand the mechanisms underlying the development of the visual system, and in the past, the cerebellum. Retinal ganglion cells from each eye project through the optic chiasm to the same and opposite side of the brain to form a circuit that implements binocular vision. We use a battery of static and dynamic microscopical techniques, cellular assays, and molecular approaches to dissect cell fate specification, axon pathfinding, and synapse formation in the establishment of this circuitry.
In our studies of axon guidance, we analyze 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. We have identified guidance receptors that regulate cell identity and projection of the ipsilateral retinal axon pathway through the optic chiasm. Recent work analyzed the guidance mechanisms for the contralateral projections. We have addressed how mechanisms of retinal axon decussation at the optic chiasm are relevant to the formation of connections of retinal axons in their first target, the lateral geniculate nucleus. We recently discovered that the ipsilateral and contralateral axon populations are segregated in the optic tract, and we are analyzing the molecular basis of this segregation and the extent to which it implements eye-specific targeting.
Complimenting our studies in axon guidance, we have identified transcription factors that regulate cell identity and guidance fate. Zic2 regulates the ipsilateral projection, by specifying a program of gene expression that includes the EphB1 receptor. Members of the Sox family regulate contralateral retinal ganglion cell fate. Recently we have been able to purify ipsi- and contralateral retinal ganglion cells and have found genes that direct differential neurogenetic patterns and gene expression in these two ganglion cell supbopulations.
A genetic model for these studies is the albino. In both humans and rodents, lack of pigment in the retinal pigment epithelium (RPE), the layer of cells underlying the retina leads to visual impairment due a decrease in the ipsilateral projection in both mouse and man. Through cell and molecular analyses of albino and pigmented RPE, we seek to identify factors allied with the melanogenic pathway and expressed in the embryonic eye that influence retinal ganglion cell specification and projection fate. Such factors may be useful in allaying the visual defects arising in albinism and other eye diseases leading to pathology of the RPE.
(sel.) Pathology: co-director, Electron Microscopy Lab; University – Tenure Review Committee (2010-2012); 2010- Dean’s Advisory Committee; Co-director, Doctoral Program in Neurobiology and Behavior (2006- (on leave 2013-2014)
, Kuwajima, T., and Wang, Q. (2014) The development of retinal decussations, IN: The Visual Neurosciences, Eds. L.M. Chalupa and J.S. Werner, MIT Press, Cambridge, MA (in press).
Kuwajima, T., Sitko, A.A., Bhansali, P., Jurgens, C., Guido, W., and Mason, C.
(2013) ClearT: a detergent- and solvent-free clearing method for neuronal and non-neuronal tissue. Development 140:1364-8. doi: 10.1242/dev.091844. PMID: 23444362.
Roffler-Tarlov, S., Liu, J.H., Naumova, E.N., Bernal-Ayala, M.M., and Mason, C.A.
(2013) L-Dopa and the albino riddle: content of L-Dopa in the developing retina of pigmented and albino mice. PLoS One. 2013;8(3):e57184. doi: 10.1371/journal.pone.0057184. Epub 2013 Mar 19. PMID: 23526936 [PubMed - in process]
Kuwijama T, Yoshida Y, Takehara N, A, Petros TJ, Kumanogoh, Jessell TM, Sakurai, T and Mason C
Optic chiasm presentation of Semaphorin6D in the context of Plexin-A1 and Nr-CAM promotes retinal axon midline crossing. Neuron 74: 676–690, May 24, 201213.
Rebsam, A., Bhansali, P, and Mason, C.A.
(2012) Eye-specific projections of retinogeniculate axons are altered in albino mice J. Neurosci. 32: 4821-4826. PMID 22492037; PMC3329942
Petros, T., Shresta, B., and Mason, C.A.
(2009) Specificity and sufficiency of EphB1 in driving the ipsilateral retinal projection, J. Neurosci. 29: 3463-3474. PMID: 20629048; PMC2930402
Petros, T.J., Rebsam, A., and Mason, C.
(2008). Retinal axon growth at the optic chiasm: To cross or not to cross. Annu Rev Neurosci 31, 295-315 PubMed PMID: 18558857.
For recent listing: http://www.ncbi.nlm.nih.gov/pubmed/?term=Mason+C+and+retina
Axon guidance in the binocular visual circuit in the mouse; Retinal ganglion cell fate specification; Mechanisms of albino visual system development – RPE factors controlling neural retinal development
Honors and Awards
1966 Phi Beta Kappa
1967 Woodrow Wilson Fellowship
1983-1987 Irma Hirschl Career Scientist Award
1982-1986 NIH Research Career Development Award
1992-1999 Jacob Javits Neuroscience Investigator Award
2006 Fellow, American Association for the Advancement of Science
2004-2008 Councilor, Society for Neuroscience
2011 Fellow Institute of Medicine
2013-2014 Society for Neuroscience, President
Committees , Council, and Professional Society Memberships
Editorial Board /Reviewer – Faculty of 1000, Frontiers in Neuroanatomy, Journal of Neuroscience, Neuron, Development. Reviewer – NIH-NINDA, NEI; MRC; Wellcome Foundation; ERC. SAB – Max Planck Institute for Neurobiology (Munich); Max Plank Florida Institute of Neuroscience.
Member – AAAS, Society for Neuroscience, Society for Developmental Biology, ARVO
axon guidance, developmental neurobiology, growth cone, optic chiasma, cell cell interaction, retina, transcription factor control of cell specification, tissue /cell culture, visual pathway, electron microscopy, histochemistry /cytochemistry