Mapping of chemosensory neuron function to uncover changes in neuronal fates

绘制化学感应神经元功能图谱以揭示神经元命运的变化

• 批准号: 10636843
• 负责人: Ray L Hong
• 金额: $ 36.25万
• 依托单位: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-02 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636843
• 关键词: Address; Adolescent; Adult; Affect; Afferent Neurons; Animals; Behavior; Behavioral; Caenorhabditis elegans; Calcium; Cells; Cellular Morphology; Chemotaxis; Clustered Regularly Interspaced Short Palindromic Repeats; Comparative Study; Complex; Cues; Data; Defect; Detection; Development; Ensure; Esthesia; Exhibits; Gene Expression; Genes; Genetic; Genetic Transcription; Genetic study; Health; Histamine; Homologous Gene; Human; Hydroxysteroid Dehydrogenases; Individual; Insect Vectors; Insecta; Ions; Knock-out; Larva; Life Cycle Stages; Mammals; Maps; Mediating; Modeling; Molecular; Nematoda; Nervous System; Neuroanatomy; Neuronal Differentiation; Neurons; Odors; Parasites; Parasitic nematode; Pathway interactions; Persons; Play; Preventive measure; Preventive treatment; Process; Publishing; Research; Research Support; Role; Sensory; Smell Perception; Sodium Chloride; System; Taste Perception; Taste preferences; Testing; Transgenes; Translating; Visualization; Zinc Fingers; behavior test; cell type; comparative; forward genetics; gene regulatory network; genome annotation; homeodomain; improved; in vivo; knock-down; mature animal; model organism; mutant; preference; reproductive; response; reverse genetics; sensor; transcription factor; transmission process; vector transmission

Project Summary Parasitic nematodes infect more than 150 million people worldwide and up to 1.3 billion people benefit from preventative treatment annually. Many parasitic nematodes require insect hosts for transmission to human hosts in their complex life cycles. We use a genetically tractable nematode Pristionchus pacificus that is associated with insects as a comparative model to study how diverse behaviors arise from a limited set of neurons. Our proposed research addresses a fundamental question on how nervous systems evolve to accommodate new behaviors, specifically how and which transcription factors are required to designate the developmental fates of chemosensory neurons in host- seeking behavior. We will use reverse genetics to target candidate transcriptional factors, known as terminal selector genes, as well as inducible transgenes to knock down neuronal function at the single cell level. We will also use forward genetics to investigate unbiasedly which genes are responsible to switch the preferences for taste and smell when the nematodes develop into reproductive adults or host-seeking infectious larvae. A detailed understanding of how neuronal remodeling affects chemosensation could reveal the basic blueprint for sensory neurons found in diverse nematodes, which could inform ways to disrupt the transmission of parasitic nematodes between insect and human hosts.

项目概要 寄生线虫感染全球超过 1.5 亿人，甚至高达 13 亿人 人们每年都受益于预防性治疗。许多寄生线虫需要 昆虫宿主在其复杂的生命周期中传播给人类宿主。我们使用一个 与昆虫相关的遗传易驯化的线虫Pristionchus pacificus 比较模型来研究有限的神经元组如何产生不同的行为。 我们提出的研究解决了一个基本问题：神经系统如何 进化以适应新的行为，特别是如何以及哪些转录因子 需要指定宿主化学感应神经元的发育命运 寻求行为。我们将使用反向遗传学来靶向候选转录 因子，称为末端选择基因，以及诱导转基因来敲除 在单细胞水平上降低神经元功能。我们还将利用正向遗传学 公正地研究哪些基因负责改变味觉偏好 当线虫发育成有生殖能力的成虫或寻找寄主时会发出气味 传染性幼虫。详细了解神经元重塑如何影响 化学感觉可以揭示多种感觉神经元的基本蓝图 线虫，这可以提供破坏寄生线虫传播的方法 昆虫和人类宿主之间。

项目成果

Evolution and Diversity of TGF-β Pathways are Linked with Novel Developmental and Behavioral Traits.

• DOI: 10.1093/molbev/msac252
• 发表时间: 2022-12-05
• 期刊: MOLECULAR BIOLOGY AND EVOLUTION
• 影响因子: 10.7
• 作者: Lo, Wen-Sui;Roca, Marianne;Dardiry, Mohannad;Mackie, Marisa;Eberhardt, Gabi;Witte, Hanh;Hong, Ray;Sommer, Ralf J.;Lightfoot, James W.
• 通讯作者: Lightfoot, James W.