Sabine Fuhrmann, Ph.D.

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.