Analysis and characterization of nervous system defects in candidate mutations resulting from a mutagenesis screen in the fruit fly, Drosophila melanogaster

• Main Author: Joanita Jasmen
• Other Authors: School of Biological Sciences
• Format: Final Year Project
• Language: English
• Published: 2009
• Subjects: DRNTU::Science::Biological sciences::Human anatomy and physiology::Neurobiology
• Online Access: http://hdl.handle.net/10356/16308
• Institution: Nanyang Technological University

Parkinson’s disease (PD) is characterised by the selective loss of dopaminergic (DA) neurons in the midbrain. A potential strategy to treat PD involves directing stem cell differentiation into DA progenitors. Before this can be achieved, there is a need to identify additional genes that regulate DA neuron differentiation. For this reason, an ethyl methanesulfonate (EMS) mutagenesis screen was conducted in Drosophila melanogaster. Analysis of the resulting pupal lethal (PL) cases revealed two mutants with longer ventral nerve cords (vnc) and three mutants with smaller brain lobes compared to control. In the remaining three cases, either additional Dopa decarboxylase (Ddc)-producing neurons or ‘leaky’ Ddc expression was observed in the brains of the mutants. Initial mapping experiments reveal that genes regulating cell division or apoptosis are associated with the appearance of small lobes while Frizzled2 (Fz2) is important in maintaining the number of Ddc-expressing neurons. In addition, attempts to disrupt the function of RNAse III enzymes gave no hint of the role of endogenous RNA interference (RNAi) in DA neuron differentiation and maintenance. Overall, the mutations generated were not found to be directly implicated to DA neuron fate specification as tyrosine hydroxylase (TH) expression pattern remained unaffected.