Molecular mechanisms driving cessation of neural crest migration and aggregation into cranial ganglia
驱动神经嵴迁移和聚集到颅神经节停止的分子机制
基本信息
- 批准号:10450672
- 负责人:
- 金额:$ 4.76万
- 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 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:ATAC-seqAddressAdhesionsAutomobile DrivingBehaviorBinding SitesCadherinsCandidate Disease GeneCell Adhesion MoleculesCellsCephalicCharacteristicsCytoskeletonData SetDestinationsDevelopmentDorsalEctopic ExpressionElementsEmbryoEnhancersEpithelialFamilial DysautonomiaFibrosisFluorescence-Activated Cell SortingGangliaGene ExpressionGenesGenetic TranscriptionGenomeGoalsHealthIn Situ HybridizationKnowledgeLeadLightMaintenanceMalignant NeoplasmsMediatingMesenchymalMolecularNeural CrestNeural Crest CellNeural tubeNeuraxisNeuroblastomaPeripheralPeripheral Nervous SystemPhasePheochromocytomaPhysical condensationPigmentsPlayPopulationProcessReactionRegulator GenesRegulatory ElementReporterRoleSkeletonStructureStructure of trigeminal ganglionTissuesTranscriptTranscriptional RegulationUntranslated RNAVertebratesXCL1 genecell typecraniofacialepithelial to mesenchymal transitionexperimental studygastrulationgenome-widein vivoinsightloss of functionmelanomamigrationneuromechanismnovelsomitogenesisspatiotemporalstem-like celltargeted treatmenttranscription factortranscriptometranscriptome sequencingtumor progressionwound healing
项目摘要
Proposal Summary
Neural crest cells are an important stem-like cell population characterized by their multipotency and
migratory ability. Originating within the forming central nervous system, neural crest cells undergo a
spatiotemporally regulated epithelial-to-mesenchymal transition (EMT) to leave the neural tube and become
migratory. They then migrate extensively throughout the developing embryo, giving rise to a wide range of
derivatives as diverse as elements of the craniofacial skeleton and peripheral nervous system. In the post-
migratory phase, neural crest cells condense into different structures, a process that involves loss of migratory
characteristics, perhaps reflecting the reverse of the EMT process. While neural crest EMT has been studied
extensively, the mechanisms underlying the condensation of neural crest cells to form final derivatives is far less
well characterized. To address this knowledge gap, we propose to identify transcriptional changes that
occur during gangliogenesis with the goal of identifying those mediating alterations in intercellular
adhesion required for neural crest condensation into peripheral ganglia. Our hypothesis is that the gene
regulatory mechanisms that play a role during peripheral ganglion formation may reflect a reversal of the EMT
process. The goal is to uncover the molecular mechanisms that drive condensation of neural crest cells into
ganglia. These may in turn lead to clues regarding the underlying cause of certain types of neurocristopathies
like familial dysautonomia and neural crest-derived cancers like neuroblastoma and pheochromocytoma.
Aim 1: RNA-sequencing of pure populations of post-migratory cranial neural crest cells: RNA-sequencing
of isolated condensing cranial neural crest cells will allow us to identify novel transcription factors and adhesion
molecules that may drive neural crest condensation into cranial ganglia.
Aim 2: Functional analysis of genes selectively upregulated upon condensation to form ganglia:
Identified upregulated genes in condensing cranial neural crest cells will be validated by in situ hybridization and
Hybridization Chain Reaction. We will then perform systematic loss-of-function and ectopic expression
experiments on selected genes to examine their role in regulating condensation into and differentiation of
peripheral ganglia.
Aim 3: Characterization of cis-regulatory elements modulating gene expression during ganglion
condensation: To identify putative enhancers driving gene expression during cranial neural crest condensation,
we will perform ATAC-sequencing to identify conserved noncoding regions in the genome that are accessible to
transcription factors during cranial neural crest condensation.
提案摘要
神经嵴细胞是一种重要的干细胞样细胞群,其特征在于其多能性,
迁移能力。神经嵴细胞起源于正在形成的中枢神经系统,
时空调节的上皮间质转化(EMT)离开神经管,
迁徙的然后,它们在整个发育中的胚胎中广泛迁移,引起广泛的免疫反应。
衍生物,如颅面骨骼和周围神经系统的元素。在后-
在迁移阶段,神经嵴细胞凝聚成不同的结构,这一过程涉及迁移的丧失。
这可能反映了EMT过程的逆转。虽然神经嵴EMT已被研究
广泛地说,神经嵴细胞凝聚形成最终衍生物的机制远不如
很好的描述。为了解决这一知识缺口,我们建议确定转录变化,
发生在神经节发生的目的是确定那些介导的细胞间的变化,
神经嵴冷凝进入外周神经节所需的粘附。我们的假设是
在外周神经节形成过程中发挥作用的调节机制可能反映了EMT的逆转
过程其目标是揭示驱动神经嵴细胞凝聚成
神经节这些可能反过来导致线索的根本原因,某些类型的神经criticies
比如家族性自主神经功能障碍和神经嵴源性癌症,比如神经母细胞瘤和嗜铬细胞瘤。
目的1:迁移后颅神经嵴细胞纯群体的RNA测序:RNA测序
分离浓缩颅神经嵴细胞将使我们能够识别新的转录因子和粘附
这些分子可能促使神经嵴凝聚到颅神经节。
目的2:在浓缩形成神经节时选择性上调的基因的功能分析:
在致密颅神经嵴细胞中鉴定的上调基因将通过原位杂交和
杂交链反应。然后我们将进行系统的功能丧失和异位表达
对选定的基因进行实验,以检查它们在调节浓缩和分化中的作用,
周围神经节
目的3:神经节细胞中调控基因表达的顺式调控元件的表征
冷凝:为了鉴定在颅神经嵴冷凝过程中驱动基因表达的推定增强子,
我们将进行ATAC测序,以确定基因组中保守的非编码区,这些区域可被
转录因子在颅神经嵴冷凝。
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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Hugo Alexander Urrutia其他文献
Hugo Alexander Urrutia的其他文献
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{{ truncateString('Hugo Alexander Urrutia', 18)}}的其他基金
Molecular mechanisms driving cessation of neural crest migration and aggregation into cranial ganglia
驱动神经嵴迁移和聚集到颅神经节停止的分子机制
- 批准号:
10309332 - 财政年份:2021
- 资助金额:
$ 4.76万 - 项目类别:
Molecular mechanisms driving cessation of neural crest migration and aggregation into cranial ganglia
驱动神经嵴迁移和聚集到颅神经节停止的分子机制
- 批准号:
10669179 - 财政年份:2021
- 资助金额:
$ 4.76万 - 项目类别:
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