Mechanisms driving cell fate specification and morphogenesis in the blastocyst
囊胚中细胞命运规范和形态发生的驱动机制
基本信息
- 批准号:10355512
- 负责人:
- 金额:$ 48.91万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-03-01 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AddressApplications GrantsAutomobile DrivingBiological ModelsBiologyCell Fate ControlCell LineageCell SeparationCellsCellular MorphologyCellular biologyCommunicationComputational BiologyCongenital AbnormalityCritical PathwaysDataDefectDevelopmentDevelopmental BiologyEmbryoEmbryonic DevelopmentEndodermEndoderm CellEnvironmentEpiblastEventFibroblast Growth FactorFoundationsGene ExpressionGenerationsGeneticGenetic ProcessesGenotypeGoalsHumanImageInner Cell MassLightLogicMaintenanceMarsupialiaMechanicsMethodsModelingModernizationMolecularMorphogenesisMusMutation AnalysisOrganOrganismPhasePopulationPositioning AttributePre-implantation Embryo DevelopmentReporterResolutionRoleSignal TransductionSomatic CellSystemSystems BiologyTherapeuticTimeTissuesbaseblastocystcell behaviorcell fate specificationcell typecellular transductioncohortdata analysis pipelinedriving behavioreggexperimental studygene regulatory networkin vivoinnovationinsightmethod developmentmouse developmentmouse geneticsmutantplacental mammalpreimplantationprogramspublic health relevancequantitative imagingself organizationthree dimensional structuretranscription factortranscriptomicszygote
项目摘要
PROJECT SUMMARY / ABSTRACT
Understanding the molecular logic that configures interactions between the transcription
factors and signaling networks that guide the development of an entire organism is arguably
one of the major challenges of modern biology, and as such, it needs good experimental
systems. The mammalian blastocyst is one such system.
Preimplantation mammalian embryo development - from the fertilized egg to the blastocyst
stage - offers a simplified and tractable model for investigating the coordination of cell fate
specification and morphogenesis at single-cell resolution across a population. The
blastocyst is a universal mammalian developmental stage and a paradigm of tissue self-
organization. Preimplantation embryo development involves two sequential binary cell fate
decisions that give rise to three cell lineages: the pluripotent epiblast (EPI) which is the
founder tissue of almost all somatic cells, and two primarily extra-embryonic lineages, the
trophectoderm (TE) and primitive endoderm (PrE). The three cell lineages of the blastocyst
are defined by their position, developmental potential, and marker expression. Gaining
insight into the mechanistic underpinnings of cell fate specification within the blastocyst,
builds on our previous findings, and is the subject of this R01 grant application.
The overarching goal of this project is to exploit mouse genetic and embryological methods
with single-cell resolution quantitative approaches, to understand how the pluripotent
epiblast (EPI) and primitive endoderm (PrE) lineages of the blastocyst form in time and
space.
By live imaging EPI and PrE cells as they emerge within the ICM population, we will
determine the dynamic cell behaviors driving lineage divergence within the ICM in
SPECIFIC AIM 1. To delineate the gene regulatory network driving these alternate fate
decisions, we will investigate the roles of NANOG and GATA6, the two transcription factors
positioned at the apex of the network in SPECIFIC AIM 2. FGF4 is the secreted signal
driving lineage divergence within the ICM and promoting EPI maturation. In SPECIFIC AIM
3 we will visualize cells transducing the FGF4 signal and investigate downstream
components of the FGF4 signaling cascade operating in the ICM. Since cell fate
specification across the ICM population is only complete concomitant with cell sorting, in
SPECIFIC AIM 4 we will seek to determine whether a cell's position impacts a its fate
choice.
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项目总结/摘要
理解在转录之间配置相互作用的分子逻辑
引导整个生物体发育的因子和信号网络可以说是
现代生物学的主要挑战之一,因此,它需要良好的实验
系统.哺乳动物的囊胚就是这样一个系统。
植入前哺乳动物胚胎发育-从受精卵到囊胚
阶段-提供了一个简化和易于处理的模型,用于研究细胞命运的协调
特定化和形态发生在整个群体中的单细胞分辨率。的
胚泡是哺乳动物普遍的发育阶段,是组织自我发育的范例,
organization.植入前胚胎发育涉及两个连续的二元细胞命运
决定产生三种细胞谱系:多能外胚层(EPI),
几乎所有体细胞的创始人组织,和两个主要的胚外谱系,
滋养外胚层(TE)和原始内胚层(PrE)。囊胚的三种细胞谱系
由它们的位置、发育潜力和标记表达来定义。获得
深入了解胚泡内细胞命运特化的机制基础,
建立在我们以前的研究结果之上,也是R 01资助申请的主题。
该项目的首要目标是利用小鼠遗传学和胚胎学方法
单细胞分辨率定量方法,以了解多能性
胚泡的上胚层(EPI)和原始内胚层(PrE)谱系及时形成,
空间
通过实时成像EPI和PrE细胞,因为它们出现在ICM群体中,我们将
确定驱动ICM内谱系分化的动态细胞行为,
具体目标1.为了描绘出驱动这些交替命运的基因调控网络
决定,我们将研究NANOG和GATA 6的作用,这两个转录因子
位于SPECIFIC AIM 2中网络的顶点。FGF 4是分泌信号,
驱动ICM内的谱系分化并促进EPI成熟。具体目标
3我们将观察转导FGF 4信号的细胞,并研究下游信号。
在ICM中操作的FGF 4信号级联的组分。因为细胞命运
ICM群体的质量标准仅在细胞分选的同时完成,
具体目标4我们将试图确定细胞的位置是否影响其命运
选择
!
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Quantitative analysis of signaling responses during mouse primordial germ cell specification.
- DOI:10.1242/bio.058741
- 发表时间:2021-05-15
- 期刊:
- 影响因子:2.4
- 作者:Morgani SM;Hadjantonakis AK
- 通讯作者:Hadjantonakis AK
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ANNA-KATERINA HADJANTONAKIS其他文献
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{{ truncateString('ANNA-KATERINA HADJANTONAKIS', 18)}}的其他基金
Mechanisms driving cell fate specification and morphogenesis in the blastocyst
囊胚中细胞命运规范和形态发生的驱动机制
- 批准号:
10112934 - 财政年份:2018
- 资助金额:
$ 48.91万 - 项目类别:
Phenotyping Early Embryonic Lethal Knockout Mice to Identify Essential Genes with Previously Uncharacterized Roles in Pre-implantation Development, Gastrulation, Turning, and Placentation
对早期胚胎致死性基因敲除小鼠进行表型分析,以确定在植入前发育、原肠胚形成、转向和胎盘着床中具有先前未表征的作用的重要基因
- 批准号:
9906060 - 财政年份:2016
- 资助金额:
$ 48.91万 - 项目类别: