Sabine Fuhrmann
Assistant Professor of Neurobiology and Anatomy and of Ophthalmology and Visual Sciences
B.S. University of Oldenburg
Ph.D. University of Freiburg, Germany
Research
Lab Goal: To understand the cellular and molecular mechanisms regulating early eye development.
During development of the vertebrate eye, complex patterning events occur which result in the generation of distinct tissue components. We have recently shown that tissues surrounding the embryonic eye are critical for controlling the development of regional patterns. The molecular signals that mediate these patterning events are, for the most part, unknown. Multiple congenital eye disorders, including anophthalmia, micropthalmia, aniridia, coloboma, and retinal dysplasia stem from disruptions in early eye development. It is thus critical to define the signals that regulate normal patterning and development of the optic vesicle (see figure). Signaling molecules like Sonic Hedgehog, TGFb family members, FGFs, and Wnts control patterning and differentiation of the neural tube. Currently, we are studying the role of these signaling molecules during early eye development. The goal of our research is to elucidate the cellular and molecular mechanisms that regulate the patterning and differentiation of ocular tissues, especially of the neural retina and retinal pigmented epithelium. An understanding of these mechanisms combined with the identification of key regulatory genes could provide important targets of intervention for the treatment of many ocular diseases.
(1) Regulation of retinal pigmented epithelium (RPE) formation in chick and mouse Several mutations affect normal RPE formation resulting in severe developmental defects such as transdifferentiation of the RPE and loss of pigmentation. Until recently, nothing was known about signals that promote induction and differentiation of the RPE. We have shown that TGFb/Activin signaling regulates optic vesicle patterning in the chick eye and we are currently investigating the role of these signals in RPE patterning in mouse. The goal is to identify novel RPE-promoting factors and to test their role during eye development using different approaches (e.g. explant cultures, degenerate PCR, in vivo-electroporation).
(2) Determine the role of Wnt/Frizzled
signaling in ocular development Since several Wnt molecules
and the appropriate receptors (Frizzleds) are expressed in the
developing vertebrate eye, we are studying the role of the Wnt/b-catenin
pathway during development of ocular tissues in chick and mouse.
To identify Wnt/b-catenin responsive
populations in the developing eye, we are characterizing transgenic
mice that express b-galactosidase under
the control of a b-catenin-responsive
promoter. We are also investigating whether Frizzled receptors
participate in the regulation of neural retina development.

Development of the vertebrate eye. Factors from surrounding tissues initiate patterning of the domains of the vertebrate optic vesicle (A), which is essential for normal eye development such as formation of the optic cup (B).
References
1. Seydewitz V, Rothermel A, Fuhrmann S, Schneider A, DeGrip WJ, Layer P, Hofmann H-D (2004) Expression of CNTF receptor a in chick violet-sensitive cones with unique morphological properties. IOVS 45(2):655-661
2. Fuhrmann S, Stark M, Heller S (2003) Expression of Frizzled genes in the developing chick eye. Mechanisms of Development/Gene Expression Patterns 3(5):659-662
3. Fuhrmann S, Grabosch K, Kirsch M, Hofmann H-D (2003) Distribution of CNTF receptor a protein in the central nervous system of the chick embryo. J Comp Neurol 461:111-122
4. Fuhrmann S, Levine EM, Reh TA (2000) Extraocular mesenchyme patterns the optic vesicle during early eye development in the embryonic chick. Development 127:4599-4609
5. Levine EM, Fuhrmann S, Reh TA (2000) Soluble factors and the development of rod photoreceptors. Cell Mol Life Science 57:224-234
6. Fuhrmann S, Chow L, Reh TA (2000) Molecular control of cellular diversification in the vertebrate retina. Results Probl Cell Differ 31:69-91


