Ophthalmic Research Symposium with Prof....

Home » The Institute » News & Events » News » News Article

Ophthalmic Research Symposium with Prof. Elisabeth Knust, MPI Dresden

The Institute for Ophthalmic Research Tübingen invited Prof. Knust from the Max-Planck Institut für Molekulare Zellbiologie und Genetik, Dresden, Germany to give a talk in the Ophthalmic Research Symposium on Wednesday, October 23th. Her talk was hosted by Bernd Wissinger and entitled „The role of cell polarity regulators in retinal development and homeostasis”.

Prof. Knust begun here talk entitled “The role of epithelial cell polarity in retinal development and homeostasis” with an introduction into the function of epithelial cells. The overall functions are very diverse and include barrier formation, secretion, morphogenesis and sensory perception. These multiple tasks require a specific morphological organization of the cell known as cell polarization or cell polarity. Hallmarks of epithelial cell polarity are distinct membrane domains (apical versus basal), tightly/adherent junctions, a polarized cytoskeleton and polarized trafficking. The distinct membrane domains allow e.g. the formation of microvilli or outer segments on the apical site as it is known for photoreceptors. To establish cell polarity, several protein complexes that have a restricted localization to the apical or basal domain of epithelial cells are required: in Drosophila, the Crumbs complex formed by Crumbs, Stardust and DPATJ and a complex formed by Bazooka, DmPar-6 and DaPKC are located on the apical site, whereas Scribble (Scrib), Discs large (Dlg) and Lethal giant larvae (Lgl) form a protein complex found in the basal domain. To emphasize the importance of these complexes, Prof. Knust presented histological data from Drosophila mutants lacking Crumbs or Scribble: (1) the loss of Crumbs affected the formation of the apical domain and enabled the invasion of basal proteins in the presumptive apical domain in epithelial cells (2) the loss of Scribble had the contrary effect and resulted in the loss of the basal domain and invasion of apical proteins into the presumptive basal region.

Prof. Knust highlighted that the crucial functions of the polarity regulators are conserved between Drosophila and vertebrates including humans. Thus, in humans, defects of these polarity regulating proteins are associated with a huge number of different disease such as cancer, Microvillus inclusion disease, skin diseases and also retinal diseases like Retinitis pigmentosa (RP) and Lebers congential amaurosis (LCA). The latter two diseases prompted Prof. Knust to focus here research also onto the retinal neuroepithelium. Using the zebrafish as vertebrate model, she investigated the function of Lgl2, a member of the Scribble complex, in the retina. She could confirm that lgl2 is not only expressed in the zebrafish epidermis but also in the zebrafish retina and here especially in the basal domain of the highly polarized photoreceptor cells. A complete loss of Lgl2 function resulted in a disturbed retinal layering and the disorganization of the OLM (outer limiting membrane) and the OPL (outer plexiform layer) in 3dpf zebrafish. These observations clearly demonstrated the relevance of Lgl2 for the formation of the basal domain in photoreceptors of the zebrafish retina.

In the last part of her talk, Prof. Knust focused onto the Crumbs protein family – key players in cell adhesion, cell shape formation and signaling. Drosophila mutants that lack Crumbs function show a progressive, light-induced retinal degeneration demonstrating the importance of Crumbs for the maintenance of photoreceptor integrity and providing additional insight into the Crumbs-association RP in humans.

Overall, Prof. Knust gave a survey on how cell polarization is established and how the loss of proper cell polarity is linked to disturbed tissue (layer) formation and maintenance.

Summary by Peggy Reuter of the Wissinger Lab - the Ophthalmic Research Symposium October Edition was hosted by Prof. bernd Wissinger.

Prof. Knust studied biology in Düsseldorf and also obtained her PhD in 1979 from the University Düsseldorf. From 1980 to 1983, she worked as a postdoctoral fellow at the Institute of Clinical Virology at the University Erlangen-München. In 1983, she moved to the University of Cologne, where she worked as an assistant Professor at the Institute of Developmental Biology, until 1988 when she became a Heisenberg fellow and continued her research at the University of Cologne and University of Colorado, Boulder/USA. In 1990, she became a full professor at the Institute of Developmental Biology at the University of Cologne and six years later, Prof. Knust became the Head of the Institute of Genetics at the Heinrich-Heine University Düsseldorf. Since 2007, Prof. Knust is Director and Research Group Leader at the Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden. The laboratory of Prof. Knust investigates the development and maintenance of epithelial cell polarity using Drosophila and zebrafish as model organism.