Temporal control of cell patterning, signaling, and movement in early embryos
早期胚胎细胞模式、信号传导和运动的时间控制
基本信息
- 批准号:10670250
- 负责人:
- 金额:$ 62.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-11 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:ActinsAdherens JunctionAnimalsBlastodermCell physiologyCellsCellular MorphologyChromatinComparative StudyCytoskeletonDataDevelopmentDominant-Negative MutationDorsalDrosophila genusEmbryoEmbryonic DevelopmentEnhancersFibroblast Growth FactorFundingGene ExpressionGene Expression RegulationGenesGenetic TranscriptionGoalsHomologous GeneHourImageLigandsMovementNF-kappa BOutputPatternProcessRegulatory ElementResearchSeriesSignal PathwaySignal TransductionSignaling MoleculeSupporting CellSystemTimeTissuesTranscriptVariantWorkcell motilitycombinatorialepithelial to mesenchymal transitionexperimental studygastrulationin vivo imaginginsightmorphogenspreimplantationprogramstranscription factor
项目摘要
Regulation of gene expression along the dorsal-ventral (DV) axis of Drosophila embryos serves as a
paradigm of developmental patterning. Comparative studies of cis-regulatory elements that
support expression along the DV axis from many research groups have made it clear that
combinatorial input into enhancers by multiple transcription factors drives distinct
spatial-outputs of gene expression. A pivotal regulator of this patterning process is the
maternally-provided transcription factor Dorsal (Dl), homolog of NFKB. Dl functions as
a morphogen to activate target gene expression in a concentration-dependent manner along
the DV axis, contributing to the initiation of zygotic gene expression at the
maternal-to-zygotic transition (MZT). Using live imaging, we quantified the Dl gradient in embryos
and found, surprisingly, that levels change not only in space but also build in time. Our
focus during the previous funding period was to study the impact of these Dl dynamics on target
gene expression using quantitative approaches involving analysis of live imaging or fixed embryo
time-series data to provide insight. In the current proposal, we follow three new and exciting
directions, which relate to the timing of cell actions in early embryos and arose as a result of
the previous work. Project 1 involves studying how broadly-expressed activators and repressors
cooperate to control the onset of zygotic gene expression during the MZT. We hypothesize that
broadly-expressed repressors are equally important to pioneer activators in the control of
chromatin accessibility and thereby also regulate initiation of zygotic gene expression. Project 2
focuses on dissecting the function of short-transcripts for long genes that are expressed
specifically in the early syncytial embryo. We hypothesize that these short transcripts act to
regulate timing of cell signaling pathway activation by functioning as dominant-negative variants
of signaling molecules. Project 3 focuses on identifying the mechanism by which FGF signaling
regulates adherens junctions (AJs) and their interaction with the actin cytoskeleton to contribute
to the first epithelial-to-mesenchymal transition (EMT) in embryos; in particular, to understand
how a degron associated with one FGF ligand, Pyramus, limits signaling time. The overarching goal
of the proposed research program is to understand how the timing of these cell activities -
patterning, signaling, and movement - are controlled in developing Drosophila embryos
and to provide general insights applicable to higher animals. While many studies have focused on
spatial outputs of gene expression, less is known about the temporal dynamics of patterning.
Drosophila embryos are a tractable system to study MZT as it occurs in 3-4 hours, in
contrast to taking days in preimplantation mammalian embryos. The Drosophila embryo is
also amenable to live in vivo imaging and tracking analyses making it well-suited to the study of
nascent transcription and cell morphology. Lastly, our proposed studies will provide general
insight into early embryo development of higher animals as many regulatory mechanisms are likely
conserved.
果蝇胚胎背腹轴(DV)基因表达调控是果蝇胚胎发育的一个重要机制
项目成果
期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Developmental Program Truncates Long Transcripts to Temporally Regulate Cell Signaling.
发育程序截断长转录本以暂时调节细胞信号传导。
- DOI:10.1016/j.devcel.2018.11.019
- 发表时间:2018
- 期刊:
- 影响因子:11.8
- 作者:Sandler,JeremyE;Irizarry,Jihyun;Stepanik,Vincent;Dunipace,Leslie;Amrhein,Henry;Stathopoulos,Angelike
- 通讯作者:Stathopoulos,Angelike
Sticking to a plan: adhesion and signaling control spatial organization of cells within migrating collectives.
坚持计划:粘附和信号传导控制迁移集体内细胞的空间组织。
- DOI:10.1016/j.gde.2019.07.003
- 发表时间:2019
- 期刊:
- 影响因子:4
- 作者:Macabenta,Frank;Stathopoulos,Angelike
- 通讯作者:Stathopoulos,Angelike
Dynamic patterning by morphogens illuminated by cis-regulatory studies.
顺式调控研究阐明了形态发生素的动态模式。
- DOI:10.1242/dev.196113
- 发表时间:2021
- 期刊:
- 影响因子:0
- 作者:Irizarry,Jihyun;Stathopoulos,Angelike
- 通讯作者:Stathopoulos,Angelike
NaNuTrap: a technique for in vivo cell nucleus labelling using nanobodies.
- DOI:10.1242/dev.199822
- 发表时间:2021-09-15
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Migrating cells control morphogenesis of substratum serving as track to promote directional movement of the collective.
迁移细胞控制基质的形态发生,作为促进集体定向运动的轨道。
- DOI:10.1242/dev.177295
- 发表时间:2019
- 期刊:
- 影响因子:0
- 作者:Macabenta,Frank;Stathopoulos,Angelike
- 通讯作者:Stathopoulos,Angelike
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Angelike Stathopoulos其他文献
Angelike Stathopoulos的其他文献
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{{ truncateString('Angelike Stathopoulos', 18)}}的其他基金
Regulation of long distance enhancer-promoter interactions by promoter-proximal elements
启动子-近端元件对长距离增强子-启动子相互作用的调节
- 批准号:
10688129 - 财政年份:2022
- 资助金额:
$ 62.31万 - 项目类别:
Regulation of long distance enhancer-promoter interactions by promoter-proximal elements
启动子-近端元件对长距离增强子-启动子相互作用的调节
- 批准号:
10536568 - 财政年份:2022
- 资助金额:
$ 62.31万 - 项目类别:
Investigating how sequentially acting cues guide long-distance cell migration in vivo within embryos
研究顺序作用线索如何引导胚胎体内的长距离细胞迁移
- 批准号:
10458611 - 财政年份:2020
- 资助金额:
$ 62.31万 - 项目类别:
Investigating how sequentially acting cues guide long-distance cell migration in vivo within embryos
研究顺序作用线索如何引导胚胎体内的长距离细胞迁移
- 批准号:
10223395 - 财政年份:2020
- 资助金额:
$ 62.31万 - 项目类别:
Investigating how sequentially acting cues guide long-distance cell migration in vivo within embryos
研究顺序作用线索如何引导胚胎体内的长距离细胞迁移
- 批准号:
10667457 - 财政年份:2020
- 资助金额:
$ 62.31万 - 项目类别:
Investigating reverse signaling by FGFs using an animal model system
使用动物模型系统研究 FGF 的反向信号传导
- 批准号:
10212438 - 财政年份:2020
- 资助金额:
$ 62.31万 - 项目类别:
Mechanisms of Broadly-Expressed Repressors in Zygotic Gene Expression in an Animal Model
动物模型中合子基因表达中广泛表达的阻遏蛋白的机制
- 批准号:
9789684 - 财政年份:2018
- 资助金额:
$ 62.31万 - 项目类别:
Deciphering when the pivotal transcription factor Dorsal exerts patterning effects using optogenetics
利用光遗传学破译关键转录因子 Dorsal 何时发挥模式效应
- 批准号:
9612309 - 财政年份:2018
- 资助金额:
$ 62.31万 - 项目类别:
Temporal control of cell patterning, signaling, and movement in early embryos
早期胚胎细胞模式、信号传导和运动的时间控制
- 批准号:
10445335 - 财政年份:2016
- 资助金额:
$ 62.31万 - 项目类别:
Developmental Progression Driving Gastrulation of the Drosophila Early Embryo
驱动果蝇早期胚胎原肠胚形成的发育进程
- 批准号:
9752601 - 财政年份:2016
- 资助金额:
$ 62.31万 - 项目类别:
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