Transcriptional control of collective cell migration

集体细胞迁移的转录控制

基本信息

  • 批准号:
    9344648
  • 负责人:
  • 金额:
    $ 31.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-09-23 至 2020-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY / ABSTRACT Critical physiological and pathological processes, such as wound healing, blood vessel formation and cancer metastasis, rely on directed collective cell migrations, whereby groups of cells collectively polarize and move together in an orderly fashion. The ability of cell collectives to migrate directionally is determined in part by the tissue-specific transcriptional inputs that define the complement of expressed genes and thus their competence to migrate. The long-term goal of this project is to understand how tissue-specific transcription regulators control the basic cellular processes underlying directed collective cell migration. To this aim, the simplified embryos of a chordate species, the ascidian Ciona intestinalis, will be used to study the migration of pre- cardiac mesoderm cells, called “trunk ventral cells” (TVCs). The TVCs provide the simplest possible model of directed collective cell migration in live embryos. On each side of the embryo, only two cells migrate together and display a clear Leader-Trailer polarity aligned with the direction of migration: the leader TVC displays a broad leading edge and more conspicuous protrusions than the trailer. It was previously established that Mesp, Fibroblast growth factor (Fgf) signaling and FoxF transcriptional inputs determine the ability of TVCs to migrate. Moreover, TVCs migrate strictly between the endodermal and ectodermal germ layers, a hallmark of mesodermal cardiac progenitors. It was determine that these surrounding tissues contribute to canalizing TVCs' innate motility towards collective polarity and directed migration. The goal of the proposed research is to understand how transcriptionally-controlled intrinsic TVC properties interface with extrinsic signals to determine collective polarity and directed migration in the embryo. Preliminary studies suggested that the gene encoding the discoidin domain receptor (Ddr) is upregulated by Mesp, FGF and FoxF transcriptional inputs in the TVCs, where it promotes adhesion to the epidermis. Using newly developed quantitative imaging methods, the detailed mechanisms controlling Ddr expression, localization and activity will be analyzed. The hypothesis that a cell-autonomous antagonism between Ddr and vascular endothelial growth factor receptor (Vegfr) signaling positions the migrating TVCs between the epidermis and endoderm will be tested. Preliminary observations suggest that Ddr promotes adhesion to the epidermis by regulating vesicle trafficking. The hypothesis that Ddr acts in Rab4/Rab11-positive endosomes to promote the recycling of integrins to the plasma membrane will be tested. Finally, the functions of regulated candidate effectors of collective migration will be studied extensively using TVC-specific CRISPR/Cas9-mediated loss-of-function assays and high-content phenotypic analyses. A provisional model of the biomolecular network controlling the subcellular processes underlying TVC behavior will be built. Particular attention will be paid to the candidate modulators of Ddr, Vegfr and integrin functions. Completion of this project will illuminate the systems' level mechanisms linking intrinsic transcriptional inputs and extrinsic signals to define cell-specific behaviors.
项目摘要/摘要

项目成果

期刊论文数量(0)
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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Lionel Christiaen其他文献

Lionel Christiaen的其他文献

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{{ truncateString('Lionel Christiaen', 18)}}的其他基金

Ninth International Tunicate Meeting
第九届国际被囊动物会议
  • 批准号:
    9398756
  • 财政年份:
    2017
  • 资助金额:
    $ 31.96万
  • 项目类别:
Regulation of muscle fate specification and cell migration in cardiogenic lineage
心源性谱系中肌肉命运规范和细胞迁移的调节
  • 批准号:
    8186167
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Cellular determinants of cardiopharyngeal multipotency and early fate choices
心咽多能性和早期命运选择的细胞决定因素
  • 批准号:
    9981188
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Regulation of early cardiopharyngeal fates specification
早期心咽命运规范的调节
  • 批准号:
    9028926
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Regulation of muscle fate specification and cell migration in cardiogenic lineage
心源性谱系中肌肉命运规范和细胞迁移的调节
  • 批准号:
    8527830
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Cellular determinants of cardiopharyngeal multipotency and early fate choices
心咽多能性和早期命运选择的细胞决定因素
  • 批准号:
    10470093
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Regulation of muscle fate specification and cell migration in cardiogenic lineage
心源性谱系中肌肉命运规范和细胞迁移的调节
  • 批准号:
    8307454
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Regulation of muscle fate specification and cell migration in cardiogenic lineage
心源性谱系中肌肉命运规范和细胞迁移的调节
  • 批准号:
    8701367
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Cellular determinants of cardiopharyngeal multipotency and early fate choices
心咽多能性和早期命运选择的细胞决定因素
  • 批准号:
    10161814
  • 财政年份:
    2011
  • 资助金额:
    $ 31.96万
  • 项目类别:
Transcriptional control of collective cell migration
集体细胞迁移的转录控制
  • 批准号:
    8323459
  • 财政年份:
    2010
  • 资助金额:
    $ 31.96万
  • 项目类别:

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