SABINE FUHRMANN
Sabine Fuhrmann
e-mail: sabine.fuhrmann@hsc.utah.edu		 Assistant Professor of Ophthalmology & Visual Science
Adjunct Assistant Professor of Neurobiology & Anatomy

Developmental Neuroscience
Molecular Neuroscience
Neurobiology of Disease
Cellular Neuroscience

Diploma in Biology 1991, University of Oldenburg; Ph.D. 1996, University of Freiburg, Germany; Postdoctoral Fellow 1997-2000, University of Washington, Seattle.

RESEARCH:

Regulation of eye development

The goal of our research is to elucidate the cellular and molecular mechanisms that regulate the patterning and differentiation of ocular tissues, specifically the neural retina and retinal pigment epithelium.

(1) Regulation of retinal pigment epithelium (RPE) development
The RPE consists of a monolayer of cuboidal, pigmented cells that is located between the retina and choroid. It is vital for growth and function of the vertebrate eye and improper development results in congenital defects such as microphthalmia, anophthalmia or a change of cell fate resulting in loss of the RPE. However, very little is known about the mechanisms that specify and maintain the RPE fate. We have evidence that the surrounding extraocular mesenchyme secretes an RPE inducer and we are currently investigating the role of TGFβ/Activin signaling as a candidate signaling pathway. Furthermore, subsequent to RPE specification, it is critical to maintain the RPE status. We recently determined that the Wnt/β-catenin pathway is required for maintaining expression of RPE regulatory genes, by directly transactivating RPE genes. Our goal is to elucidate the mechanisms by which TGFβ/Activin and Wnt/β-catenin pathways control RPE development, maintenance and regeneration. A better understanding of the processes underlying RPE development will potentially lead to therapeutic treatments for ocular diseases involving the RPE such as macular degeneration and retinitis pigmentosa and will have implications for ocular stem cell biology.

(2) Analysis of differential gene expression in chick ocular tissues
Because the neural retina and RPE are distinct tissues with very different functions, the genetic differences are likely to be established early during development. We are screening presumptive neural retina and RPE tissue at the optic vesicle stage for novel differentially expressed genes using microarrays. The long-tem goal is to test the actual function of candidate genes using in vitro and in vivo approaches in chick and mouse.

Conditional disruption of B-catenin in the embryonic mouse RPE leads to a loss of pigmentation (B; arrow) and abnormal thickening of the dorsal RPE (B; arrowhead),
an initial sign of defective RPE formation. A,C: control.

Selected Publications

Westenskow, P.D., Piccolo, S., and Fuhrmann, S. (2009) β-catenin controls differentiation of the retinal pigment epithelium in the mouse optic cup by regulating Mitf and Otx2 expression. Development, 136:2505-2510.

Fuhrmann, S., Riesenberg, A., Mathiesen, A.M., Brown, E.C., Vetter, M.L., Brown, N.L. (2009) 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., and Vetter, M.L. (2008) A nonautonomous role for retinal Frizzled-5 in regulating hyaloid vitreous vasculature development. Invest Ophthalmol Vis Sci, 49:5561-5567.

Fuhrmann, S. (2008) Wnt signaling in eye organogenesis. Organogenesis, 4(2):60-67.

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., and Fuhrmann, S. (2008) Investigation of Frizzled-5 during embryonic neural development in mouse. Developmental Dyamics, 237:1614-1626.

Levine, E.M., and Fuhrmann, S. (2008) Contribution of environmental factors to rod photoreceptor development: An update on the regulation of rod photoreceptor development. Ophthal Res Series, Visual Transduction and Non-Visual Light Perception, Tombran-Tink J, Barnstable C (Eds.), 4:3-64.

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