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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：
Pavak Kirit Shah
金额：
$ 18.99万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
https://reporter.nih.gov/project-details/10523112
关键词：
3-Dimensional Ablation Afferent Neurons Anatomy Animals Behavior Behavior Control Behavioral Biological Assay Caenorhabditis elegans Cell Lineage Cell Nucleus Cell membrane Cells Chemotaxis Chromosome Mapping Computer software Cues Development Developmental Biology Embryo Embryonic Development Esthesia Evolution Fluorescence Microscopy Future Gene Expression Gene Transfer Techniques Genetic Genetic Screening Genetic Transcription Health Hookworms Human Image Individual Invertebrates Investigation Label Lasers Link Maps Modeling Morphology Nematoda Neuroanatomy Neurons Nuclear Odors Order Coleoptera Organism Parasites Parasitic nematode Pathway interactions Pattern Penetration Persons Pheromone Physiology Postembryonic Prophylactic treatment Regulation Resolution Resource-limited setting Sensory Signal Transduction Skin Specific qualifier value Strongyloides stercoralis Systems Development Taste Perception Training Work body position cellular imaging contrast imaging convolutional neural network design embryo cell fluorescence imaging genetic manipulation insight light transmission microscopic imaging neglected tropical diseases neural neural circuit neural network neuron development neuronal cell body novel programs reconstruction response sensory system social tool vertebrate 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