Jagged-Notch and Fgf signaling: patterning the vertebrate upper face
Jagged-Notch 和 Fgf 信号:脊椎动物上表面的图案
基本信息
- 批准号:7936846
- 负责人:
- 金额:$ 3.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-18 至 2013-08-31
- 项目状态:已结题
- 来源:
- 关键词:Alagille SyndromeAnimalsApert-Crouzon syndromeCellsCongenital AbnormalityCraniofacial AbnormalitiesDataDefectDevelopmentDorsalEctopic ExpressionEmbryoFaceFishesGene ExpressionGenesGeneticGoalsHumanImageImaging TechniquesLinear ModelsLinkModelingMolecularMutationNeural CrestPathway interactionsPatientsPatternReporterResearch TrainingResolutionRoleSignal PathwaySignal TransductionSkeletonSpecific qualifier valueStagingTestingTimeTransgenic OrganismsTransplantationWorkZebrafishbasecraniofacialinsightjagged1 proteinmutantnotch proteinnovelreceptorresearch studyskeletal
项目摘要
DESCRIPTION (provided by applicant): Craniofacial abnormalities are the most common human birth defects, and yet little is known about the developmental basis that leads to mispatterning of the face. Several studies have Identified factors involved in patterning the lower (ventral) face; however, less is known about the dorsal (upper) face. In humans, mutations in Jagged and Notch have been linked to Alagille syndrome, whereas aberrant Fgf signaling results in Crouzon syndrome. As similar facial defects are observed in both Alagille and Crouzon, Notch and Fgf may be involved in a common pathway that patterns the facial skeleton. In this proposal, I investigate a novel role of Jagged-Notch and Fgf signaling in zebrafish involved in promoting dorsal facial identity. In my preliminary data, Jagged-Notch signaling promotes dorsal facial identity by repressing ventral gene expression in skeletal precursors; however, the molecular mechanism of how Notch promotes dorsal remains unknown. Thus in the first aim, I propose a model where dorsal facial identity is specified by a propagating Notch signaling wave that originates in the dorsal domain. Using a transgenic Notch reporter and high-resolution imaging, I will capture Notch activation in real time during patterning stages. In the second aim, I propose experiments that build on my initial findings that Fgf signaling also promotes dorsal identity. By using transgenic fish, in which Fgf signaling is upregulated or inhibited at specific times of development, I will determine if Fgf signaling uses similar molecular mechanisms as Notch to promote dorsal identity. In the third aim, I will test how Jagged-Notch and Fgf signaling pathways are integrated to actively promote dorsal facial identity. Here, I propose a linear and a parallel model of signal integration. In the linear model, Fgf signaling activates the Notch pathway by controlling jagib expression. In the parallel model, Fgf and Notch independently activate the same downstream targets involved in dorsal facial patterning. To test this, I will use combinations of mutants and transgenics with altered Notch and Fgf signaling to determine how these two pathways are integrated. The goal of this proposal is to investigate a novel role of Jagged-Notch and Fgf signaling in patterning the vertebrate upper face. As mutations in Jagged 1 and the Fgf receptor 2 have been linked to craniofacial defects in Alagille and Crouzon syndrome, my work in zebrafish will reveal the developmental basis by which disruption of these pathways results in facial defects in humans.
描述(由申请人提供):颅面畸形是最常见的人类出生缺陷,但对导致面部错误模式的发育基础知之甚少。几项研究已经确定了参与下(腹侧)面部图案化的因素;然而,对背侧(上)面部知之甚少。在人类中,Jagged和Notch的突变与Alagille综合征有关,而异常的Fgf信号传导导致Crouzon综合征。由于在Alagille和Crouzon中观察到类似的面部缺陷,Notch和Fgf可能参与面部骨骼模式的共同途径。在这个提议中,我调查了一个新的锯齿状缺口和FGF信号在斑马鱼参与促进背面部身份的作用。在我的初步数据中,锯齿状凹槽信号通过抑制骨骼前体中的腹侧基因表达来促进背侧面部身份;然而,凹槽如何促进背侧面部身份的分子机制仍然未知。因此,在第一个目标,我提出了一个模型,其中背面部身份指定的传播Notch信号波,起源于背域。使用转基因Notch报告基因和高分辨率成像,我将在图案化阶段真实的时间捕获Notch激活。在第二个目标,我提出的实验,建立在我的初步研究结果,FGF信号也促进背身份。通过使用转基因鱼,其中成纤维细胞生长因子信号被上调或抑制在特定的时间的发展,我将确定是否成纤维细胞生长因子信号使用类似的分子机制Notch,以促进背部的身份。在第三个目标中,我将测试锯齿状缺口和FGF信号通路是如何整合的,以积极促进背面部的身份。在这里,我提出了一个线性和并行模型的信号集成。在线性模型中,FGF信号通过控制jagib表达激活Notch途径。在平行模型中,Fgf和Notch独立地激活参与背侧面部图案形成的相同下游靶标。为了测试这一点,我将使用突变体和转基因的组合与改变Notch和Fgf信号,以确定这两个途径是如何整合。本研究的目的是研究锯齿状缺口和成纤维细胞生长因子信号在脊椎动物上面部模式化中的新作用。由于Jagged 1和Fgf受体2的突变与Alagille和Crouzon综合征的颅面缺陷有关,我在斑马鱼中的工作将揭示这些途径的破坏导致人类面部缺陷的发育基础。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Elizabeth Zuniga-Sanchez其他文献
Elizabeth Zuniga-Sanchez的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Elizabeth Zuniga-Sanchez', 18)}}的其他基金
Deciphering the molecular mechanisms in photoreceptor wiring
破译感光器布线的分子机制
- 批准号:
10617929 - 财政年份:2021
- 资助金额:
$ 3.05万 - 项目类别:
Deciphering the molecular mechanisms in photoreceptor wiring
破译感光器布线的分子机制
- 批准号:
10723128 - 财政年份:2021
- 资助金额:
$ 3.05万 - 项目类别:
Deciphering the molecular mechanisms in photoreceptor wiring
破译感光器布线的分子机制
- 批准号:
10489851 - 财政年份:2021
- 资助金额:
$ 3.05万 - 项目类别:
Deciphering the molecular mechanisms in photoreceptor wiring
破译感光器布线的分子机制
- 批准号:
10280111 - 财政年份:2021
- 资助金额:
$ 3.05万 - 项目类别:
Deciphering the molecular mechanisms in photoreceptor wiring
破译感光器布线的分子机制
- 批准号:
10654028 - 财政年份:2021
- 资助金额:
$ 3.05万 - 项目类别:
The regulation of synaptic specificity in the mammalian retina
哺乳动物视网膜突触特异性的调节
- 批准号:
10436960 - 财政年份:2020
- 资助金额:
$ 3.05万 - 项目类别:
The regulation of synaptic specificity in the mammalian retina
哺乳动物视网膜突触特异性的调节
- 批准号:
10179396 - 财政年份:2020
- 资助金额:
$ 3.05万 - 项目类别:
The regulation of synaptic specificity in the mammalian retina
哺乳动物视网膜突触特异性的调节
- 批准号:
9370779 - 财政年份:2017
- 资助金额:
$ 3.05万 - 项目类别:
Jagged-Notch and Fgf signaling: patterning the vertebrate upper face
Jagged-Notch 和 Fgf 信号:脊椎动物上表面的图案
- 批准号:
8288026 - 财政年份:2009
- 资助金额:
$ 3.05万 - 项目类别:
Jagged-Notch and Fgf signaling: patterning the vertebrate upper face
Jagged-Notch 和 Fgf 信号:脊椎动物上表面的图案
- 批准号:
8123362 - 财政年份:2009
- 资助金额:
$ 3.05万 - 项目类别:
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 3.05万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 3.05万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 3.05万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 3.05万 - 项目类别:
Discovery Early Career Researcher Award
Zootropolis: Multi-species archaeological, ecological and historical approaches to animals in Medieval urban Scotland
Zootropolis:苏格兰中世纪城市动物的多物种考古、生态和历史方法
- 批准号:
2889694 - 财政年份:2023
- 资助金额:
$ 3.05万 - 项目类别:
Studentship
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 3.05万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 3.05万 - 项目类别:
Training Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 3.05万 - 项目类别:
Continuing Grant
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 3.05万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 3.05万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)