S-Space College of Natural Sciences (자연과학대학) Dept. of Biological Sciences (생명과학부) Theses (Ph.D. / Sc.D._생명과학부)
Studies on the neural networks and genes critical for feeding behaviors in Drosophila melanogaster
초파리 먹이행동에 중추적 역할을 하는 신경네트워크와 유전자에 대한 연구
- 자연과학대학 생명과학부
- Issue Date
- 서울대학교 대학원
- feeding behavior; satiety/anorexigenic; MIP; BW; the EB; 5-HT receptors; Misato; visceral muscle
- 학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2017. 2. 정종경.
- Although feeding is affected by multiple extrinsic and intrinsic stimuli, this behavior is primarily shaped by the two hard-wired motivational states - hunger and satiety. To expand our current understanding on the neuromolecular mechanism governing the states, I performed a genetic screen using a straightforward high-throughput feeding assay to identify novel genes and neurons critical for feeding regulation in Drosophila. By analyzing a library of 224 neuron-specific GAL4 drivers and 250 RNAi lines, I discovered two groups of anorexigenic neurons that showed striking elevation of feeding when silenced, and identified a gene that affected feeding when knocked down. Silencing Myoinhibitory peptide (MIP) neurons and the corresponding gene, mip, elicited significant increases in body weight (BW) which could be completely restored by restriction of food intake, showing the tight correlation of BW and food intake regulated by MIP neurons. By contrast, activating MIP neurons markedly decreased food intake and BW, and the loss of food intake and BW was fully rescued shortly after termination of the neural activation indicating the switch-like role of MIP neurons in food intake BW regulation. By quantifying the levels of satiety using two behavioral paradigms upon silencing or activating MIP neurons, I revealed that indeed MIP neurons induce satiety to regulate food intake and ultimately BW. Another anorexigenic neuronal population marked by 48899-GAL4 displayed a series of hunger responses when silenced
indicating 48899 neurons normally induce satiety. Consistently, activating 48899 neurons reduced food intake. Among the neural structures labeled by 48899-GAL4, the ellipsoid body (EB) subsets appeared to be critical for 48899-mediated feeding regulation. By analyzing the role of five serotonin receptors present in Drosophila, I found that the potential inhibitory role of 5-HT1A in 48899 neurons to regulate food intake. Lastly, I showed that the RNAi knockdown of misato (mst) elicited dramatic hypophagia. Particularly, the intestine of the flies with the muscle-specific mst RNAi knockdown showed characteristic enlargement followed by severe damages on the visceral muscle. However, these phenotypes were fully rescued by exogenous expression of mst, indicating the specificity of mst in the tight linkage between food intake and visceral muscle fidelity. Altogether these results demonstrated that feeding behaviors can be targeted by multiple neuromolecular entry points, and provided new insights into the understanding of animal feeding behaviors especially through satiety.