The long term objective of this study is to investigate the possible role of changes in the retinal microenvironment that induce the formation of a specialized processes of photoreceptors, known as the outer segment. Little is known regarding the elements that may play a role in the inductive process, or the source from which these putative signal(s) may come. In addition, the outer segment is a labile structure that is the first element to show pathology in animal models of many disease processes. Thus, the study of elements necessary for the development of outer segments will also be important in understanding what elements may be necessary for the induction, formation, and maintenance of outer segments, and the possible design of therapeutic strategies for human degenerative retinal diseases. The following specific aims will help obtain this objective: 1) Characterize proteins in the developing IPM that may play a role in outer segment induction using histochemistry and semi-quantitative methods, 2) Study the capacity of photoreceptor cells to form outer segments as a function of age using low density cultures from staged embryos, and 3) investigate the role of cell-cell contacts, diffusible factors, and extracellular matrix molecules, in photoreceptor outer segment induction using a combination of high and density retinal cultures, aggregate cultures, and growth of cultures in conditioned medium and/or extracellular matrix-conditioned plates.
| Nowak, Roberta B; Fischer, Robert S; Zoltoski, Rebecca K et al. (2009) Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens. J Cell Biol 186:915-28 |
