REGULATION OF NEURAL CREST CELL MIGRATION BY SDF1-CXCR4 SIGNALING
SDF1-CXCR4 信号传导对神经嵴细胞迁移的调节
基本信息
- 批准号:7959957
- 负责人:
- 金额:$ 27.8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-06-01 至 2010-05-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAfferent NeuronsBMP4CXCR4 ReceptorsCXCR4 geneCardiacCellsComplexComputer Retrieval of Information on Scientific Projects DatabaseDefectDevelopmentDorsalEmbryoEmbryonic DevelopmentEmigrationsFundingGenesGrantHematopoieticHistocompatibility TestingImmigrationInstitutionInvestigationLigandsMediatingMolecularMusNervous system structureNeural CrestNeural Crest CellNeural tubeOrganPathway interactionsPatternPerinatalPeripheral Nervous SystemPhosphorylationPhysiologicalPlayPopulationRegulationResearchResearch PersonnelResourcesRoleSensorySignal TransductionSignal Transduction PathwaySiteSourceSpinal GangliaStem cellsStromal Cell-Derived Factor 1TimeTissuesUnited States National Institutes of HealthWaardenburg-Hirschsprung diseaseZebrafishcell motilitycell typechemokinechemokine receptorloss of functionmembermigrationneuron developmentprograms
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
We plan to study the role of signaling from the chemokine stromal cell-derived factor-1 (SDF-1) through its specific receptor CXCR4 in the migration of trunk neural crest cells to the dorsal root ganglia (DRG). The study will investigate the following hypotheses: [1] the chemokine guidance receptor CXCR4 is expressed in neural crest cells during migration into the DRG in distinct spatio-temporal patterns, while its activating ligand, SDF-1, is expressed along the pathways of neural crest migration; [2] loss of function of SDF-1/CXCR signaling during embryogenesis results in altered migration of neural crest cells into the developing DRG; [3] expression of the CXCR4 chemokine receptor and its activating ligand, SDF-1, is regulated by the TGF¿ superfamily members BMP4 and TGF¿1, respectively; [4] the downstream effects of SDF-1/CXCR4 signaling which govern migration of the neural crest cells to the DRG during embryogenesis, are mediated by the phosphatidyl-inositide-3 phosphorylation signal transduction pathway.
The neural crest is a progenitor cell population contributing to a multitude of cell and tissue types, including the DRG and sensory nervous system. ¿ Signaling of the chemokine SDF-1 through its specific receptor, CXCR4 is required for the migration of many stem cell and progenitor cell populations from their respective sites of emergence to the regions where they will differentiate into complex tissues and organs. Deletion of the entire CXCR4 or SDF-1 gene in mice results in perinatal lethality at approximately gestational day 18.5 due to cerebellar, cardiac and hematopoietic defects. The global objective of this research program is to determine whether the chemokine SDF-1 is required for migration of trunk neural crest cells to the DRG during embryogenesis and whether the disruption of SDF-1 signaling to its specific receptor, CXCR4, results in altered neural crest migration and/or abnormal formation of the DRG. The research program will also investigate regulation of SDF-1 and CXCR4 expression by TGF¿1 and BMP4 in the embryo during the time of neural crest cell emigration from the dorsal aspect of the neural tube and neural crest cell migration to the dorsal root ganglia. BMP and TGF¿ are two factors that play important roles in embryonic development, and regulate SDF-1 and CXCR4 expression in a variety of adult cell types in culture. Finally, the research program will investigate whether the downstream effects of SDF-1/CXCR4 signaling during embryonic neural crest cell migration to the DRG are mediated by the phosphatidyl-inositide-3 phosphorylation signal transduction pathway.
Abnormal development of the peripheral nervous system in both mice and zebrafish following functional inactivation of the SDF-1 - CXCR4 chemokine signaling axis suggests a role of CXCR4/SDF-1 in migration of trunk neural crest cells to the forming DRG during embryogenesis. However, virtually no mechanistic information is available at present. In view of the deleterious physiological defects caused by aberrant DRG and sensory neuron development in conditions such as Waardenburg-Hirschsprung Disease and WHIM, investigations of the regulation of trunk NCC migration and formation of the DRG by SDF-1-CXCR4 signaling are of potential biomedical importance.
这个子项目是众多研究子项目之一
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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Ratnam Sathiagana Seelan其他文献
Ratnam Sathiagana Seelan的其他文献
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{{ truncateString('Ratnam Sathiagana Seelan', 18)}}的其他基金
REGULATION OF NEURAL CREST CELL MIGRATION BY SDF1-CXCR4 SIGNALING
SDF1-CXCR4 信号传导对神经嵴细胞迁移的调节
- 批准号:
8360172 - 财政年份:2011
- 资助金额:
$ 27.8万 - 项目类别:
REGULATION OF NEURAL CREST CELL MIGRATION BY SDF1-CXCR4 SIGNALING
SDF1-CXCR4 信号传导对神经嵴细胞迁移的调节
- 批准号:
8167655 - 财政年份:2010
- 资助金额:
$ 27.8万 - 项目类别:
THE EFFECT OF INTERNEURON LOSS ON MINICOLUMN STRUCTURE
中间神经元损失对微柱结构的影响
- 批准号:
7720697 - 财政年份:2008
- 资助金额:
$ 27.8万 - 项目类别:
THE EFFECT OF INTERNEURON LOSS ON MINICOLUMN STRUCTURE
中间神经元损失对微柱结构的影响
- 批准号:
7381932 - 财政年份:2006
- 资助金额:
$ 27.8万 - 项目类别:
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