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Studies on the neural networks and genes critical for feeding behaviors in Drosophila melanogaster : 초파리 먹이행동에 중추적 역할을 하는 신경네트워크와 유전자에 대한 연구
DC Field | Value | Language |
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dc.contributor.advisor | 정종경 | - |
dc.contributor.author | 민수홍 | - |
dc.date.accessioned | 2017-07-14T00:53:46Z | - |
dc.date.available | 2017-07-14T00:53:46Z | - |
dc.date.issued | 2017-02 | - |
dc.identifier.other | 000000142146 | - |
dc.identifier.uri | https://hdl.handle.net/10371/121466 | - |
dc.description | 학위논문 (박사)-- 서울대학교 대학원 : 생명과학부, 2017. 2. 정종경. | - |
dc.description.abstract | 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 | - |
dc.description.abstract | 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. | - |
dc.description.tableofcontents | Background 1
Materials and Methods 15 Results 28 PART 1 A genetic screen identified candidate neurons and genes critical for food intake using a high-throughput feeding assay 29 Introduction 30 Developing a high-throughput feeding assay 38 Identification of candidate GAL4 and RNAi lines by a genetic screen using GAL4-UAS system 42 PART 2 MIP pathway regulates body weight via controlling satiety 46 Introduction 47 Silencing MIP neurons increased food intake and BW 49 TNT expression in MIP neurons blocks MIP secretion 56 Adult-specific silencing MIP neurons still increased BW 59 Silencing MIP neurons also increased abdominal fat storage 63 BW increase of MIP>TNT flies was mediated by elevated food intake 69 Activation of MIP neurons decreased food intake and BW 72 Activation of MIP neurons made flies leaner 75 MIP-GAL4 was expressed in the central nerve system (CNS) and gastrointestinal tract 77 MIP was expressed in the central nerve system (CNS) 80 MIP expression responded to activation of MIP neurons and starvation 84 Functional examination of the AL and SEZ expression by MIP 87 MIP expression in MIP-GAL4 neurons was required for BW regulation 91 Cha-GAL80 fully rescued the defective BW increase of MIP>TNT flies 94 A subset of MIP neurons in the CNS was responsible for BW regulation 96 Generation of a null mutation for mip 100 Mip was necessary for food intake and BW control 102 MIP was required for MIP neuron-mediated BW regulation 106 MIP regulates BW independently of the sex peptide receptor (SPR) 108 MIP neurons mediate olfactory anorexigenic responses 109 Behavioral paradigm to measure satiety using PER 113 Suppressing MIP pathway made flies lack satiety 115 Activating MIP pathway induced satiety 119 PART 3 A subset of the ellipsoid body neurons labeled by 48899-GAL4 negatively regulates food intake 121 Introduction 122 Satiated flies with silenced 48899 neurons still overfed 123 Activation of 48899 neurons induces hypophagia 125 Mimicry of hunger states induced by silencing 48899 neurons 127 Visualization of 48899 neurons 130 The PI cells of 48899 neurons were DH44-expressing neurons 132 The DH44 neurons were dispensable for 48899 neuron-mediated feeding control 134 EB R4 neurons were responsible for the feeding phenotype 137 Additional GAL4 lines that label EB R4 neurons elicited hyperphagic phenotype when silenced 140 Serotonin receptors might function in 48899 neurons to mediate feeding 142 48899 neurons responding to internal energy level 145 PART 4 Misato is required for the visceral muscle maintenance for intestinal homeostasis in Drosophila 147 Introduction 148 RNAi knockdown of mst in the muscle tissue elicits decreased food intake 150 Aged mef2>mst RNAi flies exhibit enlarged intestine 152 Newly-born mef2>mst RNAi flies do not show the intestinal phenotypes 157 Phenotypical analysis on aged mef2>mst RNAi flies 159 Mef2-GAL4 is expressed in the outer layer of the visceral muscle 165 The visceral muscle is responsible for the intestinal phenotype 167 The visceral muscle is damaged in the aged mef2>mst RNAi flies 172 Aged mef2>mst RNAi flies showed increased apoptosis in the intestine 174 Intestine of aged mef2>mst RNAi flies showed increased level of ISCs 176 Exogenous expression of mst in the muscle fully rescued the intestinal defects of mef2>mst RNAi flies 179 Mst functions in the visceral muscle independently of the TCP- 1 tubulin chaperone complex 181 Discussion 183 The identity of the neural pathway post-synaptic to MIP neurons 184 Is MIP pathway the sole mediator for signaling satiety 186 The mechanism underlying the MIP pathway-mediated satiety 187 The relationship of MIP and 48899 pathways in signaling satiety 187 The role of 48899 neurons in feeding choices 188 Conclusions 189 1. A genetic screen identified candidate neurons and genes critical for feeding control using a high-throughput feeding assay 189 2. MIP pathway maintains a constant BW through signaling satiety 190 3. A subset of the EB neurons labeled by 48899-GAL4 suppresses food intake 192 4. Misato is required for the visceral muscle maintenance for intestinal homeostasis in Drosophila 194 Reference 195 Abstract in Korean/국문초록 205 | - |
dc.format | application/pdf | - |
dc.format.extent | 28371264 bytes | - |
dc.format.medium | application/pdf | - |
dc.language.iso | en | - |
dc.publisher | 서울대학교 대학원 | - |
dc.subject | feeding behavior | - |
dc.subject | satiety/anorexigenic | - |
dc.subject | MIP | - |
dc.subject | BW | - |
dc.subject | the EB | - |
dc.subject | 5-HT receptors | - |
dc.subject | Misato | - |
dc.subject | visceral muscle | - |
dc.subject.ddc | 570 | - |
dc.title | Studies on the neural networks and genes critical for feeding behaviors in Drosophila melanogaster | - |
dc.title.alternative | 초파리 먹이행동에 중추적 역할을 하는 신경네트워크와 유전자에 대한 연구 | - |
dc.type | Thesis | - |
dc.contributor.AlternativeAuthor | Soohong Min | - |
dc.description.degree | Doctor | - |
dc.citation.pages | 207 | - |
dc.contributor.affiliation | 자연과학대학 생명과학부 | - |
dc.date.awarded | 2017-02 | - |
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