The utility and caveat of split-GAL4s in the study of neurodegeneration.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Fly Pub Date : 2023-12-01 DOI:10.1080/19336934.2023.2192847

Luca Stickley, Rafael Koch, Emi Nagoshi

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引用次数: 2

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.

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分裂- gal4s在神经退行性疾病研究中的应用和警告。

帕金森病（PD）是第二常见的神经退行性疾病，困扰着超过1%的60岁人群 y及以上。黑质致密部多巴胺能神经元的缺失是其特征性运动症状的主要原因。使用黑腹果蝇和其他模型系统进行的研究为帕金森病的发病机制提供了很多见解。然而，人们对某些细胞类型在帕金森病中选择性易变性的原因知之甚少。在这里，我们描述了一种在果蝇中识别与帕金森病相关的遗传背景中易受伤害的神经元亚群的方法，使用分裂-GAL4驱动程序，其能够对少量定义的细胞群体进行遗传操作。我们在富含亮氨酸重复激酶2（LRRK2）连接的家族性帕金森病模型中鉴定了靶向选择性易损神经元的分裂-GAL4系，证明了这种方法的实用性。在与衰老相关的研究中，我们还展示了对分裂-GAL4系统的一个意想不到的警告：GAL4标记细胞数量的年龄依赖性增加。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fly 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Fly is the first international peer-reviewed journal to focus on Drosophila research. Fly covers a broad range of biological sub-disciplines, ranging from developmental biology and organogenesis to sensory neurobiology, circadian rhythm and learning and memory, to sex determination, evolutionary biology and speciation. We strive to become the “to go” resource for every researcher working with Drosophila by providing a forum where the specific interests of the Drosophila community can be discussed. With the advance of molecular technologies that enable researchers to manipulate genes and their functions in many other organisms, Fly is now also publishing papers that use other insect model systems used to investigate important biological questions. Fly offers a variety of papers, including Original Research Articles, Methods and Technical Advances, Brief Communications, Reviews and Meeting Reports. In addition, Fly also features two unconventional types of contributions, Counterpoints and Extra View articles. Counterpoints are opinion pieces that critically discuss controversial papers questioning current paradigms, whether justified or not. Extra View articles, which generally are solicited by Fly editors, provide authors of important forthcoming papers published elsewhere an opportunity to expand on their original findings and discuss the broader impact of their discovery. Extra View authors are strongly encouraged to complement their published observations with additional data not included in the original paper or acquired subsequently.