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.

项目摘要 寄生线虫感染了全球超过1.5亿人，高达13亿 人们每年受益于预防治疗。许多寄生线虫需要 昆虫宿主以复杂的生命周期传播到人类宿主。我们使用一个 与昆虫作为一种相关的遗传性危险线虫pristionchus pacificus 比较模型研究了有限的神经元集产生的多种行为。 我们提出的研究解决了一个关于神经系统如何的基本问题 进化以适应新的行为，特别是如何和哪些转录因素 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 因素，称为末端选择器基因以及可诱导的转基因敲击 在单细胞水平上向下神经元功能。我们还将使用远期遗传学 公正地调查哪些基因负责切换口味的偏好 当线虫发展成生殖成年人或寻求宿主时，闻到了 传染性幼虫。对神经元重塑如何影响的详细理解 化学敏化可能揭示了在多种多样的感觉神经元的基本蓝图 线虫，可以告知破坏寄生线虫传播的方法 在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.