An integrative cellular blueprint of vertebrate tissue development

脊椎动物组织发育的综合细胞蓝图

基本信息

  • 批准号:
    10001627
  • 负责人:
  • 金额:
    $ 75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-15 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary / Abstract Every animal begins as a single cell. How this cell ultimately gives rise to a vertebrate animal possessing millions to trillions of cells, each specialized to perform specific functions in a variety of organ systems, remains a fundamental question in biology. Until now, in toto capture of the collective cellular behaviors that generate the vertebrate body plan has not been possible. We have assembled a team with complementary expertise in developmental genetics, tissue patterning, imaging, and quantitative biology that will synergize to take lineage analysis in vertebrates to an entirely new level. We will utilize the unique strengths of the zebrafish, combined with recent advances in genetic fate mapping techniques, high-resolution, whole-animal 4D microscopy, and computational methodologies to derive its complete lineage map. Our proposed approaches are precise, enabling prospective and retrospective lineage analyses, and they are visual, enabling direct identification and quantification of cell behaviors. We have developed indelible marking systems to laser-target single cells in the embryo and permanently activate reporter gene expression. Clonal analysis beyond the embryo will involve inducible Cre recombinases and single/multicolor Cre-releasable reporter transgenes. Our toolset will allow any cell of interest and its progeny to be followed for life. By deriving a library of thousands of labeled animals, we will create unprecedented access to the biography of each organ. To complement our cellular tagging approaches, we will develop imaging platforms to elucidate the entire progeny sets of labeled clones and their tissue distribution. We will also develop novel computational methods to track clones across development and to generate a digitized map that recapitulates the cellular dynamics that underlie the adult body plan. Clonal data sets will be utilized to develop probabilistic models to infer how proliferation and differentiation dynamics give rise to observed lineage restriction. Collectively, this massive technological achievement will yield templates of organ morphogenesis that we will make facile for any user to access, visualize, and manipulate. These body plan reconstructions can be employed as a baseline for interpreting cell lineage decisions in response to tissue damage, genetic manipulation, or malignancy.
项目摘要/摘要

项目成果

期刊论文数量(0)
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Zhirong Bao其他文献

Zhirong Bao的其他文献

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{{ truncateString('Zhirong Bao', 18)}}的其他基金

An integrative cellular blueprint of vertebrate tissue development
脊椎动物组织发育的综合细胞蓝图
  • 批准号:
    10474400
  • 财政年份:
    2018
  • 资助金额:
    $ 75万
  • 项目类别:
An integrative cellular blueprint of vertebrate tissue development
脊椎动物组织发育的综合细胞蓝图
  • 批准号:
    10241925
  • 财政年份:
    2018
  • 资助金额:
    $ 75万
  • 项目类别:
WormGUIDES: A Resource for Global Understanding in Dynamic Embryonic Systems
WormGUIDES:动态胚胎系统全局理解的资源
  • 批准号:
    9358881
  • 财政年份:
    2013
  • 资助金额:
    $ 75万
  • 项目类别:
An integrated system to monitor complex tissues at single-cell resolution
以单细胞分辨率监测复杂组织的集成系统
  • 批准号:
    8704126
  • 财政年份:
    2012
  • 资助金额:
    $ 75万
  • 项目类别:
An integrated system to monitor complex tissues at single-cell resolution
以单细胞分辨率监测复杂组织的集成系统
  • 批准号:
    9101424
  • 财政年份:
    2012
  • 资助金额:
    $ 75万
  • 项目类别:
An integrated system to monitor complex tissues at single-cell resolution
以单细胞分辨率监测复杂组织的集成系统
  • 批准号:
    8549292
  • 财政年份:
    2012
  • 资助金额:
    $ 75万
  • 项目类别:
An integrated system to monitor complex tissues at single-cell resolution
以单细胞分辨率监测复杂组织的集成系统
  • 批准号:
    9114130
  • 财政年份:
    2012
  • 资助金额:
    $ 75万
  • 项目类别:
An integrated system to monitor complex tissues at single-cell resolution
以单细胞分辨率监测复杂组织的集成系统
  • 批准号:
    8414001
  • 财政年份:
    2012
  • 资助金额:
    $ 75万
  • 项目类别:
Systematic Multi-scale Analysis of Tissue Morphogenesis
组织形态发生的系统多尺度分析
  • 批准号:
    9311707
  • 财政年份:
    2011
  • 资助金额:
    $ 75万
  • 项目类别:
The Ubiquitin-Proteasome System in Metazoan Embryogenesis
后生动物胚胎发生中的泛素-蛋白酶体系统
  • 批准号:
    8303404
  • 财政年份:
    2011
  • 资助金额:
    $ 75万
  • 项目类别:

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