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Research

The nervous system is comprised of an astounding collection of distinct cell types, which must be generated at the appropriate place and time and in correct numbers during development. How are these cell fate decisions controlled? The retina is one of the most accessible parts of the central nervous system and has served as a wonderful model for addressing how cell fate is determined. We are using both Xenopus laevis and mouse to define at a molecular level the essential steps in the life of a progenitor cell as it progresses towards a specific retinal neuron fate.

An important theme of our work is to understand the interplay between transcription factors that regulate neural differentiation in the retina and extrinsic signaling pathways that modulate their expression or function, resulting in changes in gene expression and thus in cell fate. For example, we have been investigating the mechanisms by which proneural transcription factors promote retinal neuron differentiation, and how they contribute to the ordered sequence of retinal histogenesis. We find that both the expression and activity of these factors are controlled multiple signaling pathways. For example, we recently showed that Wnt signaling through the Fz5 receptor regulates the expression of Sox2, which is required for neural competence and the expression of proneural factors in the developing eye. Ultimately, the goal is to reveal general principles governing the development of neural stem cells and progenitors, which may inform efforts to harness these cells for the treatment of disease and injury of the nervous system.

In that vein, we are investigating the mechanisms underlying a devastating degenerative disease of the retina, namely glaucoma, which is characterized by progressive loss of retinal ganglion cells (RGCs) leading to blindness. We are focusing our efforts on understanding the changes that take place at early stages of disease using an inbred mouse strain that develops glaucoma-like pathology (DBA/2J). We find that glaucoma shares many of the hallmark features of other neurodegenerative diseases, including significant involvement of microglia. We have also found early down-regulation of key regulatory genes within RGCs themselves, and are determining how their loss contributes to changes in the viability of RGCs. Because of these common features, glaucoma may offer a tractable system for understanding how neural tissue responds to stress or injury and degenerates over time.

Selected Publications

Search Pubmed for Monica Vetter's lab publications

• Willardsen, M.I., Suli, A., Marsh-Armstrong, N., Chien, C-B., Brown, N.L., Moore, K.B., and Vetter, M.L. (2009) Temporal regulation of Ath5 gene expression during Xenopus eye development. Dev Biol. 326:471-481.
• Agathocleous M, Iordanova I, Willardsen MI, Xue XY, Vetter ML, Harris WA, Moore KB (2009) A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina. Development, 136:3289-3299
• Fuhrmann S, Riesenberg AN, Mathiesen AM, Brown EC, Vetter ML, Brown NL. (2008) Characterization of a transient TCF/LEF-responsive progenitor population in the embryonic mouse retina. Invest Ophthalmol Vis Sci., 50:432-440.
• Zhang J, Fuhrmann S, Vetter ML. (2008) A non-autonomous role for retinal Frizzled-5 in regulating hyaloid vitreous vasculature development. Invest Ophthalmol Vis Sci., 49:5561-5567.
• Riesenberg, A.N., Le, T.T., Willardsen, M.I., Blackburn, D.C., Vetter, M.L., Brown, N.L. (2008) Pax6 regulation of Math5 during mouse retinal neurogenesis. Genesis. 47:175-187.
• Soto, I., Oglesby, E., Buckingham, B.P., Son, J.L., Roberson, E.D., Steele, M.R., Inman, D.M., Vetter, M.L., Horner, P.J., Marsh-Armstrong, N. (2008) Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model. J. Neurosci., 28:548-61.
• Bosco A., Inman, D.M., Steele, M.R., Wu, G.,  Soto, I., Marsh-Armstrong, N., Hubbard, W.C., Calkins, D.J., Horner, P.J., Vetter, M.L. (2008) Reduced retina microglial activation and improved optic nerve integrity with minocycline treatment in the DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci. 49:1437-46.
• Buckingham, B.P., Inman, D.M., Lambert, W., Oglesby, E., Calkins, D.J., Steele, M.R., Vetter, M.L., Marsh-Armstrong, N., Horner, P.J.  (2008) Progressive ganglion cell degeneration precedes neuronal loss in an animal model of glaucoma. J. Neuroscience. 28:2735-44.
• Burns, C.J, Zhang, J., Brown, E.C., Van Bibber, A.M., Van Es, J., Clevers, H., Ishikawa, T., Taketo, M.M., Vetter, M.L., Fuhrmann, S. (2008) Investigation of Frizzled-5 during embryonic neural development in mouse. Developmental Dynamics, 237(6):1614-1626.
• Steele, M.R., Inman, D.M., Calkins, D.J., Horner, P.J. and Vetter M.L.  (2006) Microarray Analysis of Retinal Gene Expression in the DBA/2J Model of Glaucoma. Invest Ophthalmol Vis Sci, 47:977-985.

Recent Reviews and book chapters

• Moore, K.B. and Vetter, M.L. (2007) Retinal development (chapter). Principles of Developmental Genetics, Ed. Sally Moody. Elsevier, Inc.
• Vetter, M.L. and Dorsky, R. Neural differentiation (chapter), Developmental Neurobiology, 4th Edition. Eds. Mahendra Rao and Marcus Jacobson. Plenum Press, 2005.
• Vetter, M.L. and Levine E. (2004) Adult retinal stem cells. In: Adult Stem Cells (ed: Turksen, K.) Humana Press, Totowa, NJ.
• Logan, M.A. and Vetter, M.L. (2004) Do-it-yourself tiling: dendritic growth in the absence of homotypic contacts. Neuron, 43:439-440.
• Van Raay T.J. and Vetter M.L., (2004) Wnt/frizzled signaling during vertebrate retinal development. Dev Neurosci., 26:352-358.
• Vetter, M.L. (2003) Methylation gets SMRT: Functional insights into Rett Syndrome. Dev. Cell. 5:359-360.
• Hutcheson, D.A. and Vetter, M.L. (2002) Transgenic approaches to retinal development and function in Xenopus laevis. Methods, vol. 28(4), 402-410.