The utility and caveat of split-GAL4s in the study of neurodegeneration. Issue 1 (31st December 2023)

• Record Type: Journal Article
• Authors: Stickley, Luca; Koch, Rafael; Nagoshi, Emi
• Is Part Of: Fly. Volume 17:Issue 1(2023)
• Publication Date: 2023-12-31
• Subjects: Split-GAL4 -- neurodegeneration -- LRRK2 -- Parkinson's disease -- dopaminergic neurons -- PAM neurons; Drosophila -- Periodicals; 595.77
• DOI: 10.1080/19336934.2023.2192847
• Languages: English
• ISSNs: 1933-6934

Abstract

ABSTRACT: Parkinson's disease (PD) is the second most common neurodegenerative disorder, afflicting over 1% of the population of age 60 y and above. The loss of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) is the primary cause of its characteristic motor symptoms. Studies using Drosophila melanogaster and other model systems have provided much insight into the pathogenesis of PD. However, little is known why certain cell types are selectively susceptible to degeneration in PD. Here, we describe an approach to identify vulnerable subpopulations of neurons in the genetic background linked to PD in Drosophila, using the split-GAL4 drivers that enable genetic manipulation of a small number of defined cell populations. We identify split-GAL4 lines that target neurons selectively vulnerable in a model of leucine-rich repeat kinase 2 ( LRRK2 )-linked familial PD, demonstrating the utility of this approach. We also show an unexpected caveat of the split-GAL4 system in ageing-related research: an age-dependent increase in the number of GAL4-labelled cells.