Cell lineage-based investigation of chemosensory neuron development
基于细胞谱系的化学感应神经元发育研究
基本信息
- 批准号:10523112
- 负责人:
- 金额:$ 18.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-12-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAblationAfferent NeuronsAnatomyAnimalsBehaviorBehavior ControlBehavioralBiological AssayCaenorhabditis elegansCell LineageCell NucleusCell membraneCellsChemotaxisChromosome MappingComputer softwareCuesDevelopmentDevelopmental BiologyEmbryoEmbryonic DevelopmentEsthesiaEvolutionFluorescence MicroscopyFutureGene ExpressionGene Transfer TechniquesGeneticGenetic ScreeningGenetic TranscriptionHealthHookwormsHumanImageIndividualInvertebratesInvestigationLabelLasersLinkMapsModelingMorphologyNematodaNeuroanatomyNeuronsNuclearOdorsOrder ColeopteraOrganismParasitesParasitic nematodePathway interactionsPatternPenetrationPersonsPheromonePhysiologyPostembryonicProphylactic treatmentRegulationResolutionResource-limited settingSensorySignal TransductionSkinSpecific qualifier valueStrongyloides stercoralisSystems DevelopmentTaste PerceptionTrainingWorkbody positioncellular imagingcontrast imagingconvolutional neural networkdesignembryo cellfluorescence imaginggenetic manipulationinsightlight transmissionmicroscopic imagingneglected tropical diseasesneuralneural circuitneural networkneuron developmentneuronal cell bodynovelprogramsreconstructionresponsesensory systemsocialtoolvertebrate embryos
项目摘要
Project Summary
Signaling from chemosensory neurons regulates changes in animal physiology and behavior in response to
environmental and social cues. Sensory neuroanatomy is so broadly conserved in nematodes that, based on
morphology and cell body position, functionally homologous chemosensory neurons have been identified
across widely divergent nematode genera, including the well-studied free living nematode Caenorhabditis
elegans, the skin-penetrating human parasite Strongyloides stercoralis, and the predatory nematode Pristionchus
pacificus.
Despite this homology, little is known about the conservation of the developmental and genetic programs that
produce individual chemosensory neurons and maintain or differentiate their function. To what extent do
anatomically homologous neurons share conserved chemosensory function? And to what extent does
anatomical homology reflect a common developmental program? We will answer these questions by mapping
the cell lineages that give rise to chemosensory neurons, determining the extent to which positionally
homologous chemosensory neurons are specified by conserved transcriptional regulators, and identifying
conserved chemosensory function. We will achieve this by developing a novel 3D style transfer convolutional
neural network (stCNN) to automate the identification of major cellular features such as the nucleus and cell
membrane in transmitted light imaging with differential interference contrast (DIC). We will then use this tool
to reconstruct the embryonic lineages of S. stercoralis and P. pacificus, map the expression of known regulators of
chemosensory neural identity to these lineages, and assess the conservation of function between homologous
chemosensory neurons by performing laser cell ablations and single-worm chemotaxis assays.
This work has direct relevance to human health, since chemosensation regulates many aspects of development,
physiology, and behavior in S. stercoralis and other human-parasitic nematodes. Parasitic nematodes infect over
a billion people worldwide and cause some of the most common and devastating neglected tropical diseases,
particularly in low-resource settings. Our multi-species approach will allow us to determine which aspects of
nematode chemosensory system development and function are broadly conserved, and which contain species-
specific adaptations that drive species-specific behaviors, including parasitic behaviors. Furthermore, the
automated reconstruction of cell lineages from DIC images will be an enabling tool of broad value. The ability
to map new developmental lineages without transgenesis will be especially transformative in the study of
human-parasitic nematodes such as hookworms that are not amenable to genetic manipulation, and can be
extended to non-nematode species, including early-stage vertebrate embryos.
项目总结
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Pavak Kirit Shah其他文献
Pavak Kirit Shah的其他文献
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{{ truncateString('Pavak Kirit Shah', 18)}}的其他基金
Lineage-Specific Mechanisms of Cell Cycle Timing Control
细胞周期计时控制的谱系特异性机制
- 批准号:
10715965 - 财政年份:2023
- 资助金额:
$ 18.99万 - 项目类别:
Cell lineage-based investigation of chemosensory neuron development
基于细胞谱系的化学感应神经元发育研究
- 批准号:
10373822 - 财政年份:2021
- 资助金额:
$ 18.99万 - 项目类别:
Understanding the Developmental Mechanisms that Ensure Robustness in Neuronal Patterning
了解确保神经元模式稳健性的发育机制
- 批准号:
10004225 - 财政年份:2019
- 资助金额:
$ 18.99万 - 项目类别:
Understanding the Developmental Mechanisms that Ensure Robustness in Neuronal Patterning
了解确保神经元模式稳健性的发育机制
- 批准号:
10251027 - 财政年份:2019
- 资助金额:
$ 18.99万 - 项目类别:
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