Genetic and epigenetic regulation of cranial neural crest differentiation
颅神经嵴分化的遗传和表观遗传调控
基本信息
- 批准号:10442617
- 负责人:
- 金额:$ 42.6万
- 依托单位:
- 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:2021-07-01 至 2023-02-01
- 项目状态:已结题
- 来源:
- 关键词:ATAC-seqAbnormal CellAffectBindingBinding SitesBiological ModelsBiologyCartilageCell Differentiation processCell LineageCellsCephalicChondrocytesChromatinChromatin Remodeling FactorCleft LipCleft PalateCompetenceCongenital AbnormalityCraniofacial AbnormalitiesDNADNA BindingDataDefectDevelopmentDevelopmental BiologyDiseaseDue ProcessEVI1 geneEmbryoEnhancersEpigenetic ProcessEtiologyExhibitsFamilyFoundationsGATA1 geneGene ExpressionGene Expression RegulationGene TargetingGenesGeneticGenetic TranscriptionGenomeGenomicsGenotypeGoalsGrowthHistonesHumanIndividualKnock-outKnowledgeLimesLinkMissionModificationMusMutationNatureNeural CrestNeural Crest CellPalatePathway interactionsPenetrancePhenotypePlayProcessProtein FamilyProteinsPublic HealthRegulationResearchRoleSignal TransductionSiteSpecific qualifier valueStructural Congenital AnomaliesSyndromeTestingTherapeuticTimeTissuesUnited States National Institutes of HealthWNT Signaling PathwayZebrafishbonecell typechromatin modificationcraniofacialcraniofacial complexcraniofacial structuredesigndisabilityepigenetic regulationgain of functiongene networkgene regulatory networkhistone methyltransferasehuman diseaseinsightmutantneuromechanismnovelparalogous genestem cellstranscription factortranscriptometranscriptome sequencing
项目摘要
How cells become specified and differentiate at the correct time and place is a fundamental question in
developmental biology. Cranial neural crest cells (cNCCs) are an excellent model system to understand this
process due to the multipotent nature of the progenitor cells, generally unrestricted developmental potential
with known lineage and derivatives, and defined gene regulatory networks. In addition to the gene networks,
epigenetic regulators can affect the expression of numerous target genes and may help to explain the
differences in penetrance and phenotype between individuals with the same genotype. This is important since
defects in neural crest development underlie many human congenital birth defects, such as cleft lip with or
without palate and many craniofacial syndromes. Thus, understanding the genetic and epigenetic regulators in
cNCC development is key to understanding how cell fate is determined. We hypothesize that PRDM
paralogs regulate global gene expression by regulating downstream targets oppositely, including Wnt
pathway components, to control the timing of cartilage/bone differentiation within the cNCC lineage.
The rationale for the proposed studies is that an in depth understanding of normal cNCC development will
provide insights into normal biology and the etiology of neural crest-associated birth defects, many of which are
thought to arise from cNCC abnormalities. We will test this hypothesis in the following specific aims: 1) Test
the hypothesis that PRDM proteins act upstream of Wnt signaling to control the timing of cNCC
differentiation into chondrocytes. We will test the hypothesis PROM paralog activity is required in cNCCs
cell autonomously upstream of Wnt signaling to promote differentiation of chondrocytes. 2) Test the
hypothesis that Prdm3 and Prdm16 genetically interact to regulate cNCC gene expression and
chromatin accessibility. In Aim 2, hypothesis that Prdm3 and Prdm16 genetically interact to control gene
expression via regulating transcription and chromatin modification specifically at cNCC and Wnt gene targets.
3) Test the hypothesis that Prdm3 regulates global gene expression by controlling the timing of
genomic accessibility of Prdm16. In Aim 3, we will test the hypothesis that loss of Prdm3 leads to global
alterations in chromatin state at cNCC progenitor genes via changes in binding of Prdm16 throughout the
genome, which controls the liming of cNCC differentiation into chondrocytes. Together, these studies will
reveal basic information of how cNCCs differentiate into specific cell types during development. The results of
this proposal have the potential to reveal important new insights into cNCC development and how these
processes go wrong in disease, with the hope of providing a foundation for the design of therapeutic strategies
for neural crest associated birth defects.
细胞是如何在正确的时间和地点被指定和分化的
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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Kristin Artinger其他文献
Kristin Artinger的其他文献
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{{ truncateString('Kristin Artinger', 18)}}的其他基金
The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells
表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用
- 批准号:
10805033 - 财政年份:2023
- 资助金额:
$ 42.6万 - 项目类别:
Reprogramming myogenic regulatory factors in RMS to promote differentiation and halt growth
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- 批准号:
10682281 - 财政年份:2023
- 资助金额:
$ 42.6万 - 项目类别:
Genetic and epigenetic regulation of cranial neural crest differentiation
颅神经嵴分化的遗传和表观遗传调控
- 批准号:
10817293 - 财政年份:2023
- 资助金额:
$ 42.6万 - 项目类别:
Genetic and epigenetic regulation of cranial neural crest differentiation
颅神经嵴分化的遗传和表观遗传调控
- 批准号:
10316019 - 财政年份:2021
- 资助金额:
$ 42.6万 - 项目类别:
The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells
表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用
- 批准号:
10352461 - 财政年份:2021
- 资助金额:
$ 42.6万 - 项目类别:
The role of epigenetic modifiers in regulating the developmental plasticity of cranial neural crest cells
表观遗传修饰剂在调节颅神经嵴细胞发育可塑性中的作用
- 批准号:
10211467 - 财政年份:2021
- 资助金额:
$ 42.6万 - 项目类别:
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The mechanisms regulating actin dynamics and polarized membrane transport during cell migration
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The mechanisms regulating actin dynamics and polarized membrane transport during cell migration
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10693336 - 财政年份:2018
- 资助金额:
$ 42.6万 - 项目类别:
Function of chromatin modifiers in cranial neural crest development
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8913662 - 财政年份:2015
- 资助金额:
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