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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳俊宏(Chun-Hong Chen) | |
| dc.contributor.author | Yen-Wei Lai | en |
| dc.contributor.author | 賴彥瑋 | zh_TW |
| dc.date.accessioned | 2022-11-23T08:58:18Z | - |
| dc.date.available | 2021-11-03 | |
| dc.date.available | 2022-11-23T08:58:18Z | - |
| dc.date.copyright | 2021-11-03 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-10-27 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79332 | - |
| dc.description.abstract | "神經幹細胞 (neural stem cells) 能產生出各種不同類型的神經元進而組成一個具有層次性的神經系統，隨後再依規律性的修改生成出神經迴路 (neural circuits)，因而增加了神經的可塑性 (neural plasticity)，所以有許多的研究會著重於神經元要如何生長及精確化而達到個體成年所需的神經元。果蠅的學習與記憶中樞-蘑菇體 (mushroom body) 包含了3種不同的神經元：γ神經元、α’/β’神經元和α/β神經元，並且作為模式系統去研究細胞命運特化 (cell fate specification) 和神經再塑性 (neural remodeling) 是如何發生的，TGF-β訊息 (transforming growth factor β (TGF-β) signaling)、蛻皮激素訊息 (Ecdysone signaling) 和Maternal gene required for meiosis (Mamo) 已被報導說同時參與在細胞命運決定和神經元神經突修剪 (neurite pruning) 的兩個過程中，因此當下仍不清楚外在訊息和內部訊息的真正功能是什麼。 此刻，我會證明帶有人類流感凝集素 (human influenza hemagglutinin, HA) 標籤的第一型TGF-β受體：Babo (TGF-β receptor, Babo) 在新生成的神經元中具有高表現量，並且持續表現在蘑菇體的γ神經元中，所以以上結果視為TGF-β訊息可能在神經元神經突的生長和γ神經元的軸突修剪 (axon pruning) 所必須的條件。另外，我描述了一個全新功能關於TGF-β訊息聯合蛻皮激素訊息如何編織γ神經元的成熟化 (neural maturation)，在成蛹階段開啟表現並標示著亞型蘑菇體神經元之晚期標誌，當受到蛻皮激素受體 (Ecdysone receptor, EcR) 和Babo的RNA干擾 (RNA interference, RNAi) 處置時就不會啟動並表現在蘑菇體神經元中，也就意味著在成蟲階段的γ神經元可能還維持著幼蟲之不成熟狀態而不是成蟲之成熟狀態。最後，Mamo異構體 (Mamo isoforms) 被γ和α’/β’神經元所需要而去調控變態 (metamorphosis) 期間的細胞命運特化。MamoD~G異構體主要表現在於α’/β’神經元且主導著蘑菇體α’/β’專一性的細胞標誌。除了細胞標誌調控之外，α’/β’和α/β之間的背葉 (dorsal lobe) 排斥現象 (repulsion) 是在MamoD~G異構體驅使細胞表層分子Semaphorin 1a (Sema-1a) 的控制之下而成的；相較之下MamoH,I異構體主要存在於γ神經元且引導著蘑菇體γ專一性的細胞標誌。引人注目的是MamoH,I異構體的敲落 (knockdown) 造成修剪缺失，然而敲落所有Mamo異構體卻造成選擇性的修剪/不完全的修剪缺失 (select pruning/semi-pruning defect)。 總結，我讓內生性的TGF-β受體：Babo的表現圖樣顯現出來並詮釋了TGF-β訊息促使神經元藉由幼蟲至成蟲階段的轉變使得細胞本體的成熟化，再來專一性的Mamo異構物最終在後分裂時期之已分化的神經元中調控及維持細胞命運特化。 " | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T08:58:18Z (GMT). No. of bitstreams: 1 U0001-2710202108424900.pdf: 6073232 bytes, checksum: e0b4ce32fd3bf872821bc270c77031f3 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試委員會審定書 p.1 致謝 p.2 中文摘要 p.3 Abstract p.5 Table of Contents p.7 List of Tables p.10 List of Figures p.11 Abbreviations p.14 Chapter 1. Introductions p.17 1. Introduction of Drosophila mushroom body p.17 2. Cell fate specification in Drosophila p.19 3. Neural remodeling in Drosophila p.23 Chapter 2. Visualization of Endogenous Type I TGF-β Receptor Baboon in the Drosophila Brain p.29 Results p.31 1. Commercially available Babo antibodies fail to faithfully detect Babo expression p.31 2. Visualization of endogenous Babo expression using a baboHA knock-in fly p.32 3. Babo::HA is primarily expressed in neuropils and nerve fibers of the brain. p.33 4. Utilization of the baboHA fly to validate babo as a miR-34 target gene. p.35 Discussion p.37 Chapter 3. Drosophila hormones control transitional changes from the larval state to the adult matured state in differentiated neurons p.39 Results p.42 1. Mutations of chinmo, EcR and mamo display a similar morphological phenotype but not the marker expression in γ neurons p.42 2. TGF-β signaling associated with Ecdysone signaling erases the larval γ neuronal identity and confers the adult γ neuronal identity through mamo p.43 3. LOF of mamo but not TGF-β signaling and Ecdysone signaling fails to inhibit the α/β neuron-specific marker expression in γ neurons p.45 4. Overexpression of Mamo-F/G but not Mamo-H/I partially restores the γ and α’/β’ neuronal identity in the chinmo mutation p.46 Discussion p.48 Chapter 4. Mamo isoforms specialize terminal fate specification in late state of differentiated neurons p.51 Results p.54 1. The expression patterns of endogenous MamoD~G::HA and MamoH,I::HA in developmental MB neurons p.54 2. Specific Mamo isoforms determine different marker expression in MB subtype-specific neurons p.55 3. Mamo isoforms differentially regulate the morphology of MB neurons p.59 Discussion p.62 1. Spatial patterning of Mamo isoforms as terminal fate regulators in MB neurons p.62 2. The process of cell fate specification in neural development p.65 Materials and Methods p.67 References p.71 Tables p.81 Figures p.95" | |
| dc.language.iso | zh-TW | |
| dc.title | 果蠅TGF-β訊息傳遞和Mamo在已分化的蘑菇體神經元中調控神經元的成熟化和命運特化 | zh_TW |
| dc.title | Drosophila TGF-β signaling pathway and Mamo in neural maturation and fate specification of differentiated mushroom body neurons | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 游宏祥(Hung-Hsiang Yu) | |
| dc.contributor.oralexamcommittee | 溫進德(Hsin-Tsai Liu),高智飛(Chih-Yang Tseng),林書葦 | |
| dc.subject.keyword | 蘑菇體,細胞命運特化,神經元成熟化,TGF-β訊息,蛻皮激素訊息,Mamo異構體, | zh_TW |
| dc.subject.keyword | mushroom body,cell fate specification,neural maturation,TGF-β signaling,Ecdysone signaling,Mamo isoforms, | en |
| dc.relation.page | 136 | |
| dc.identifier.doi | 10.6342/NTU202104306 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-10-28 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 分子與細胞生物學研究所 | zh_TW |
| 顯示於系所單位： | 分子與細胞生物學研究所 | |
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