MACS: A genetic labeling tool to depict the complete neuroblast lineage of all neurons in individual Drosophila brains

MACS：一种基因标记工具，用于描述单个果蝇大脑中所有神经元的完整神经母细胞谱系

• 批准号: 8831944
• 负责人: Dawen Cai
• 金额: $ 19.43万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8831944
• 关键词: Address; Adult; Alleles; Animal Behavior; Animal Model; Animals; Arrhythmia; B-Lymphocytes; Behavior; Brain; Cardiac conduction system; Cell Count; Cell Lineage; Cells; Code; Data; Defect; Development; Developmental Process; Disease; Drosophila genus; Embryo; Fishes; Functional disorder; Gene Mutation; Genetic; Genetic Recombination; Goals; Image; In Situ; Individual; Inherited; Label; Lead; Life; Lymphocyte; Maps; Microscopy; Mus; Neural Crest; Neurons; Outcome; Positioning Attribute; Process; Rattus; Research; Resolution; Scheme; Severe Combined Immunodeficiency; Staging; Stem cells; System; Techniques; Technology; Time; TimeLine; Transgenic Animals; Variant; Work; base; brain tissue; cell type; density; design; exhaust; fly; neural circuit; neuroblast; neurogenesis; novel; public health relevance; relating to nervous system; sex; stem; stem cell biology; success; tool; two-photon

 DESCRIPTION: During development, stem/progenitor cells replicate and differentiate into many lineages, which give rise to precise number and subtypes of cells. Defects in lineage development can cause severe developmental diseases. Currently, the state-of-the-art lineage analysis uses mosaic labeling techniques to study one or a few lineages at a time to avoid ambiguity. While the small number of highlighted cells can be investigated extensively, complications in the unlabeled adjacent lineages are hidden from analysis. The ability of unambiguously labeling large number of lineages in situ is highly desired, since it is extremely exhausting, if not impossible to use the available tools to study the precise spatial-temporal relationship of all related lineages in one animal. We propose to develop a two-photon compatible multispectral and subcellular-coding system (MACS), which permits unambiguous labeling of large number of cell lineages in the same animal. We will validate MACS by mapping all of the ~100 neural lineages in single Drosophila central brain and depict the developmental processes of all Drosophila embryo neural lineages precisely in space and time. If success, MACS can be easily adapt to other transgenic animal models, including fish, mouse and rat. MACS will create new opportunities in lineage studies, such as investigating lineage variations among individuals, and between hypomorphic alleles or different sex; as well as cell non-autonomous effects of gene mutations in stem/progenitor cells.

 描述：在开发过程中，茎/祖细胞复制并分化为许多谱系，从而导致细胞的精确数量和亚型。谱系发育中的缺陷会导致严重的发育疾病。当前，最新的谱系分析使用镶嵌标记技术一次或几个谱系来避免歧义。虽然可以广泛研究少量突出的细胞，但未标记的相邻谱系中的并发症隐藏在分析中。高度期望明确标记大量谱系的能力，因为它非常疲惫，即使不是不可能使用可用工具来研究一只动物中所有相关谱系的精确时空关系。我们建议开发一个两光子兼容的多光谱和亚细胞编码系统（MAC），该系统允许大量细胞谱系的明确标记我们将通过映射单个Drosophila中心脑中所有〜100个神经谱系的〜100个神经谱系来验证MAC，并描述所有DarosophiLa neurone intryeal intimene intimene intimene intimene intimene intimise intimene intimene intimise intimises in precisis precisis precisis。如果成功，MAC可以很容易地适应其他转基因动物模型，包括鱼，小鼠和大鼠。 MAC将在谱系研究中创造新的机会，例如研究个体之间的谱系变化，以及型型等位基因或性别不同；以及基因突变在茎/祖细胞中的细胞非自主作用。