Regulation of neuroectoderm morphogenesis by Nodal signaling programs
Nodal 信号传导程序对神经外胚层形态发生的调节
基本信息
- 批准号:10606406
- 负责人:
- 金额:$ 4.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-03-01 至 2025-02-28
- 项目状态:未结题
- 来源:
- 关键词:AffectAnencephaly and spina bifida X linkedAnteriorAutomobile DrivingBehaviorBlastodermCandidate Disease GeneCell CommunicationCellsChildhoodComplexCongenital AbnormalityCoupledDataDevelopmentEmbryoEmbryonic DevelopmentEndodermEnsureEventFutureGenesGeneticGenetic TranscriptionGerm LayersIndividualIntercalated CellKnowledgeLigandsLiteratureMesodermModelingMorphogenesisNeural FoldNeural Tube ClosureNeural Tube DefectsNeural tubeNeuroectodermNodalOrganismPlayPregnancyPrevalenceProcessRegulationResearchRoleSeriesSeveritiesShapesSignal PathwaySignal TransductionSignaling MoleculeSpecific qualifier valueSpinal CordSpinal DysraphismSpontaneous abortionTechniquesTestingTimeTissuesTransgenic OrganismsVertebratesZebrafishblastomere structurebrain shapecell motilitychordinconstitutive active receptorembryo cellgastrulationgene functionin vivoin vivo Modelinnovationknock-downloss of functionmorphogensmortalitynoveloptogeneticsoverexpressionpolarized cellprogramsreceptorresponsetranscriptome sequencingvertebrate embryos
项目摘要
Summary
Embryonic development is a series of tightly regulated events that build a single cell into a complex organism. A
key milestone in early embryonic development is gastrulation, when the body plan is first shaped by the behaviors
of thousands of individual cells. However, how these cells communicate to ensure proper morphogenesis is not
completely understood. Mesoderm and neuroectoderm (NE, future neural tube) tissue morphogenesis is driven
by convergence and extension (C&E), when cells intercalate to simultaneously narrow and elongate the body
axis and bring the neural folds together to ensure proper neural tube closure. Disruptions in these highly
conserved cell movements can result in neural tube defects that affect many pregnancies worldwide. Nodal is a
well conserved signaling pathway that is active during gastrulation and most well-known for the role it plays in
mesoderm and endoderm specification in vertebrates. However, little is understood about the role of Nodal in
C&E morphogenesis independent of mesoderm formation, particularly in NE. By utilizing zebrafish ex vivo and
in vivo models, I will study the role of Nodal specifically in morphogenesis independent of its better-known
function during tissue specification. To examine the role of Nodal underlying NE morphogenesis, I can
independently analyze NE extension using ex vivo zebrafish blastoderm explants, naïve clusters of embryonic
cells that form all three germ layers and undergo C&E morphogenesis in response to exogenous Nodal signaling.
An early peak of Nodal signaling in explants promotes mesoderm extension and specification. However,
preliminary data from our lab demonstrated that a relatively delayed peak of Nodal signaling promotes NE-
specific C&E morphogenesis that is independent of its role in mesoderm specification. This suggests that the
temporal regulation of Nodal regulates NE-specific morphogenesis. Based on my promising preliminary data, I
hypothesize that Nodal signaling activates a novel, temporally regulated, NE-specific transcriptional program
that drives C&E morphogenesis independent of mesoderm specification. To test this hypothesis, I propose 3
aims: Aim 1 will investigate the role of temporal Nodal signaling dynamics in NE-specific morphogenesis using
optogenetic Nodal receptors to precisely manipulate signaling in embryonic explants. In Aim 2, I will restore
Nodal signaling specifically within the NE of Nodal-deficient zebrafish embryos using innovative transgenic lines
to determine whether Nodal can drive in vivo NE extension in the absence of mesoderm. Finally, in Aim 3 I will
perform over expression and knock-down of temporally regulated candidate genes to determine if they are
drivers of NE-specific extension both explants and in vivo. This proposal will define the foundational knowledge
on the primary role of Nodal in NE-specific morphogenesis, disruptions in which may contribute to neural tube
defect prevalence and severity.
总结
项目成果
期刊论文数量(0)
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Alyssa Nicole Emig其他文献
Alyssa Nicole Emig的其他文献
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