Development of the Visual System
University of Calgary
Department of Cell Biology and Anatomy
Genes and Development Research Group
University of Calgary
3330 Hospital Drive N.W
T2N 4N1, Canada
Key to understanding brain development is determining how distinct neurons are produced and connect up with specific partners. While it is clear that the environment of the developing brain provides instructions in the form of extrinsic chemical signals, we are a long way from knowing, for even one type of neuron in the central nervous system (CNS), the complement of signals required. The accessibility of the visual system, with its small number of easily identified cell types, makes it an excellent place to study signals involved in CNS development. Currently, our research is focused on the development of retinal ganglion cells (RGCs). RGCs are the only neurons to extend axons out of the eye into the optic nerve, and are the final output cells of the retinal circuit. We are attempting to understand the signaling that leads to RGC production and integration into the neural circuitry of the visual system. Our model is Xenopus laevis, where we take advantage of in vitro and in vivo approaches that make this system amenable to systematic functional exploration. Since proteins and how they function are conserved across species, this research may eventually lead to therapies to reconnect damaged optic or brain nerves. My research program explores how extrinsic and intrinsic signals influence RGCs and their axons. In the next 5 years our research will focus primarily on determining how RGCs axons navigate to the optic tectum, and what mechanisms drive their specification. We believe that with the advent of the post-genomic era it will be critical to have well characterized and easily manipulable vertebrate assay systems, such as we have with the Xenopus visual system, to rapidly ascertain the role of individual genes in the development of specific cell types and neural circuitry. We want to understand the signals governing the production and differentiation of RGCs. Our lab has demonstrated that signaling by fibroblast growth factors receptor (FGFR) ligands is involved in almost all aspects of RGC development. We showed in vivo that an FGF signal promotes RGC production (Patel et al., 2000), and is necessary and sufficient for the development of rod photoreceptors (McFarlane et al., 1998). We have also identified FGFR ligands as controlling distinct aspects of the morphological differentiation of RGCs (Lom et al., 1998; McFarlane et al., 1995, 1996). Taken together, our studies have led to the novel insight that a single growth factor receptor family participates in several aspects of the development of a cell.