Comparative approaches to the study of physiology: Drosophila as a physiological tool

Abstract

Numerous studies have detailed the extensive conservation of developmental signaling pathways between the model system, Drosophila melanogaster, and mammalian models, but researchers have also profited from the unique and highly tractable genetic tools available in this system to address critical questions in physiology. In this review, we have described contributions that Drosophila researchers have made to mathematical dynamics of pattern formation, cardiac pathologies, the way in which pain circuits are integrated to elicit responses from sensation, as well as the ways in which gene expression can modulate diverse behaviors and shed light on human cognitive disorders. The broad and diverse array of contributions from Drosophila underscore its translational relevance to modeling human disease.

Fig. 1.

Life cycle and comparison with two vertebrate models. A: life cycle of Drosophila melanogaster. B: comparative length of time per generation and relative cost to maintain the same number of animals between Drosophila, zebrafish, and mouse.

Fig. 2.

The Gal4-UAS bipartite transgenic system. A line encoding the yeast transcription activator protein Gal4 is crossed with a UAS line carrying the Upstream Activation Sequence; Gal4 specifically binds to this sequence to activate gene transcription. The temporal and spatial expression is directed by promoter or enhancer sequences upstream of Gal4, and the progeny will correspondingly express the gene downstream of the UAS sequences.

Fig. 3.

Heart rate decreases with increasing age in a sexually dimorphic manner. The heart rates of age-matched male and female wild-type (Canton S) flies were compared over time. n = 40 individuals for each age (1, 3, 5, 10 or 15 days old). Individual heart rates were the average of 5 intervals of 15 s each with 15 s between each interval. Statistically significant differences indicated by asterisks over lines covering the bars. ***P < 0.001, Students t-test.

Fig. 4.

Recruitment of dopamine neurons into the stress response circuitry is dependent on sex and level of sexual maturity. A: sexually mature male and females were assayed for time spent freezing following a 24-h exposure to paraquat (oxidative) stress. Three-way ANOVA (genotype × sex × stress) P < 0.001, two-way ANOVA (sex × stress) P < 0.05 for elav^C155/w¹¹¹⁸ and P < 0.01 for 854/THK, ANOVA (stress) **P < 0.01, *P < 0.05. B: sexually immature and mature females were assayed for frequency of freezing bouts following a 24-h exposure to paraquat stress. Three-way ANOVA (genotype × age × stress) P < 0.001, two-way ANOVA, P < 0.05 for both, ANOVA (stress) ***P < 0.001. elav^C155/w¹¹¹⁸, control; 854/THK, targeted knockdown in dopamine synthesis in a subset of dopamine neurons within the mushroom bodies. n = 45.