Analysis of Dscam1 diversity in regulating dendritic morphology of Lobula Plate Tangential Cells

Claussen, Jing (2014): Analysis of Dscam1 diversity in regulating dendritic morphology of Lobula Plate Tangential Cells. Dissertation, LMU München: Fakultät für Biologie

Abstract

In arthropods like Drosophila, Down syndrome cell adhesion molecules (Dscam1) exhibit enormous molecular diversity. A single Dscam1 gene encodes a large superfamily of neuronal cell recognition proteins that control neuronal outgrowth and anatomy. A comparable function is exhibited by the vertebrates DSCAMs of which only few isoforms exist. However, it is largely unknown, if and how this function of Dscams affects neuronal function and the control of behavior by the nervous system. In this thesis, I employed an arsenal of genetic techniques to perturb the expression level of Dscam1 isoforms in directionally selective Lobula Plate Tangential Cells (LPTCs). LPTCs of the Vertical (VS) and the Horizontal System (HS) were chosen as a model system because of their well-documented anatomy, role in information processing and behavior. Though, only little is known about the developmental mechanisms and molecular factors controlling the morphogenesis and wiring of these cells. The central aim of my study thus is to reveal a possible role of Dscam1 in the growth and development of the complex dendrites of in particular HS cells. Furthermore, my work aims at establishing a novel model system for integrated studies on the development and function of LPTCs by genetic manipulations of Dscam1 expression. My results demonstrate that Dscam1 is expressed broadly in the fly visual system including HS-cells (immunolabeling of the conserved intracellular domain). Loss of Dscam1 function and reduced isoform diversity consistently elicited misrouting and self-crossings of neurites in LPTC dendrites. In contrast, misexpression of selected single Dscam1 isoforms caused a severe reduction in the size and branching complexity of LPTC dendrites. The dendritic gain-of-function phenotype (ectopic expression of the Dscam1 isoform 11.31.25.1) was strongly dependent on the time of onset of misexpression during development. These results demonstrate that Dscam1 contributes to the development of LPTC dendrites. This system can now be used to (A) address a possible role of Dscam1 in the function of neurons and circuitries and (B) to address the interplay of anatomy and function of LPTC dendrites. In further side projects I aimed at the development of additional genetic tools for the investigation of the role of LPTCs in behavior and for studies on the wiring of LPTCs to the presynaptic circuitry. I established a heat-shock protocol for the ablation of specified LPTCs by RicinA expression and I generated a fly line for the expression of TN-XXL (a genetically encoded calcium biosensor) in small cell clusters or individual cells. Finally, I participated in efforts to establish a virus based retrograde labeling method in Drosophila.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Lobula Plate Tangential Cells, Dscam1, Morphogenesis
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Fakultät für Biologie
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 11. November 2014
• 1. Bericht­erstatter:in: Borst, Alexander