Mapping of chemosensory neuron function to uncover changes in neuronal fates

项目摘要 寄生线虫感染全球超过1.5亿人， 人们每年都从预防性治疗中受益。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 一种遗传上易处理的线虫，与昆虫有关， 比较模型来研究不同的行为是如何从一组有限的神经元中产生的。 我们提出的研究解决了一个基本问题，即神经系统如何 进化以适应新的行为，特别是如何以及哪些转录因子 是指定宿主体内化学感受神经元的发育命运所必需的- 寻求行为。我们将使用反向遗传学靶向候选转录 因子，称为末端选择基因，以及诱导型转基因敲 在单细胞水平上降低神经元的功能。我们还将利用正向遗传学， 无偏见地调查哪些基因负责改变对味道的偏好 当线虫发育成成虫或寻找寄主时， 感染性幼虫详细了解神经元重塑如何影响 化学感觉可以揭示感觉神经元的基本蓝图， 线虫，这可能会提供破坏寄生线虫传播的方法 昆虫和人类宿主之间的关系

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.