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Unraveling Neuronal Development Through Novel Optogenetic and Genetic Tools
Unraveling Neuronal Development Through Novel Optogenetic and Genetic Tools
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211150918
- ISBN
- 9798382839752
- DDC
- 574
- 저자명
- Xu, Yineng.
- 서명/저자
- Unraveling Neuronal Development Through Novel Optogenetic and Genetic Tools
- 발행사항
- [Sl] : Cornell University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 319 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-12, Section: B.
- 주기사항
- Advisor: Han, Chun.
- 학위논문주기
- Thesis (Ph.D.)--Cornell University, 2024.
- 초록/해제
- 요약Neuron development is a highly orchestrated process that involves the precise coordination of cellular events, molecular signals, and environmental cues. This intricate process lays the foundation for the formation of functional neural circuits, allowing for proper information processing and communication within the nervous system. Understanding the mechanisms underlying neuron development is crucial for unraveling the complexities of brain function and for advancing our knowledge of neurological disorders and potential therapeutic interventions. To dissect the process of neuron development, optogenetics, with its ability to provide precise spatiotemporal manipulation of protein activity, offers a tremendous opportunity to investigate the complex signaling networks in developmental processes. In my dissertation research, I conducted a comprehensive investigation into both extrinsic and intrinsic factors during neuron development. The study focused on three main areas: understanding the response of neurons to nutrient stress, elucidating the role of terminal selectors in determining neuron identity post-mitotically, and developing optogenetics and CRISPR tools for studying neuron development. In the first phase of my research, my colleagues and I demonstrated that somatosensory neurons in the Drosophila peripheral nervous system exhibit organ sparing during nutrient stress. Sensory dendrites preferentially grow compared to non-neural tissues, resulting in dendrite overgrowth. These neurons exhibit lower levels of the stress sensor FoxO, leading to a milder suppression of Tor signaling and no marked induction of autophagy. Preferential dendrite growth enhances animal responses to sensory stimuli, potentially providing a survival advantage under environmental challenges.Next, I identified H6-like-homeobox (Hmx) and Cut as terminal selectors for class II (C2) and III (C3) da neurons, respectively, in Drosophila dendritic arborization (da) sensory neurons. Cut is constantly expressed in C3da neurons to inhibit Hmx expression and maintain C3da identity, while Hmx is required in C2da neurons to suppress Cut expression. Loss of each transcription factor results in upregulation of the other, leading to neuron type conversion.To further advance my research, I developed an innovative optogenetics system, OptoTrap, to manipulate endogenous proteins. I demonstrated that OptoTrap effectively traps GFP-tagged endogenous proteins of diverse sizes, subcellular locations, and functions, allowing for the manipulation of protein function in neurons and epithelial cells. Illumination conditions can be fine-tuned to achieve graded phenotypes and dissect the roles of proteins such as kinesin heavy chain (Khc) and αTubulin84B in dendrite morphogenesis.Besides, together with colleagues, I improved the CRISPR-TRiM tool by optimizing multiplexed gRNA design, enhancing gRNA efficiency in somatic tissues and the germline. I also developed methods to label mutant cells in tissue-specific mutagenesis using co-CRISPR reporters. Additionally, I created genetic reagents for converting Gal4 drivers into tissue-specific Cas9 lines through HACK.In summary, this dissertation underscored the delicate and intricate processes involved in the development of neurons and represented my efforts in advancing the tools to study neuronal development in Drosophila.
- 일반주제명
- Biology
- 일반주제명
- Neurosciences
- 일반주제명
- Genetics
- 키워드
- Optogenetics
- 키워드
- Neurons
- 기타저자
- Cornell University Genetics Genomics and Development
- 기본자료저록
- Dissertations Abstracts International. 85-12B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211150918
■006m o d
■007cr#unu||||||||
■020 ▼a9798382839752
■035 ▼a(MiAaPQ)AAI30817455
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a574
■1001 ▼aXu, Yineng.▼0(orcid)0000-0002-4473-4052
■24510▼aUnraveling Neuronal Development Through Novel Optogenetic and Genetic Tools
■260 ▼a[Sl]▼bCornell University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a319 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-12, Section: B.
■500 ▼aAdvisor: Han, Chun.
■5021 ▼aThesis (Ph.D.)--Cornell University, 2024.
■520 ▼aNeuron development is a highly orchestrated process that involves the precise coordination of cellular events, molecular signals, and environmental cues. This intricate process lays the foundation for the formation of functional neural circuits, allowing for proper information processing and communication within the nervous system. Understanding the mechanisms underlying neuron development is crucial for unraveling the complexities of brain function and for advancing our knowledge of neurological disorders and potential therapeutic interventions. To dissect the process of neuron development, optogenetics, with its ability to provide precise spatiotemporal manipulation of protein activity, offers a tremendous opportunity to investigate the complex signaling networks in developmental processes. In my dissertation research, I conducted a comprehensive investigation into both extrinsic and intrinsic factors during neuron development. The study focused on three main areas: understanding the response of neurons to nutrient stress, elucidating the role of terminal selectors in determining neuron identity post-mitotically, and developing optogenetics and CRISPR tools for studying neuron development. In the first phase of my research, my colleagues and I demonstrated that somatosensory neurons in the Drosophila peripheral nervous system exhibit organ sparing during nutrient stress. Sensory dendrites preferentially grow compared to non-neural tissues, resulting in dendrite overgrowth. These neurons exhibit lower levels of the stress sensor FoxO, leading to a milder suppression of Tor signaling and no marked induction of autophagy. Preferential dendrite growth enhances animal responses to sensory stimuli, potentially providing a survival advantage under environmental challenges.Next, I identified H6-like-homeobox (Hmx) and Cut as terminal selectors for class II (C2) and III (C3) da neurons, respectively, in Drosophila dendritic arborization (da) sensory neurons. Cut is constantly expressed in C3da neurons to inhibit Hmx expression and maintain C3da identity, while Hmx is required in C2da neurons to suppress Cut expression. Loss of each transcription factor results in upregulation of the other, leading to neuron type conversion.To further advance my research, I developed an innovative optogenetics system, OptoTrap, to manipulate endogenous proteins. I demonstrated that OptoTrap effectively traps GFP-tagged endogenous proteins of diverse sizes, subcellular locations, and functions, allowing for the manipulation of protein function in neurons and epithelial cells. Illumination conditions can be fine-tuned to achieve graded phenotypes and dissect the roles of proteins such as kinesin heavy chain (Khc) and αTubulin84B in dendrite morphogenesis.Besides, together with colleagues, I improved the CRISPR-TRiM tool by optimizing multiplexed gRNA design, enhancing gRNA efficiency in somatic tissues and the germline. I also developed methods to label mutant cells in tissue-specific mutagenesis using co-CRISPR reporters. Additionally, I created genetic reagents for converting Gal4 drivers into tissue-specific Cas9 lines through HACK.In summary, this dissertation underscored the delicate and intricate processes involved in the development of neurons and represented my efforts in advancing the tools to study neuronal development in Drosophila.
■590 ▼aSchool code: 0058.
■650 4▼aBiology
■650 4▼aNeurosciences
■650 4▼aGenetics
■653 ▼aOptogenetics
■653 ▼aNeurons
■690 ▼a0306
■690 ▼a0317
■690 ▼a0369
■71020▼aCornell University▼bGenetics, Genomics and Development.
■7730 ▼tDissertations Abstracts International▼g85-12B.
■790 ▼a0058
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160142▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
