Growth Factor Signaling in Intestinal Development
肠道发育中的生长因子信号传导
基本信息
- 批准号:7261417
- 负责人:
- 金额:$ 26.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-09-01 至 2009-06-30
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelApoptosisApoptoticBiochemicalCell LineCell ProliferationCellsCultured CellsDevelopmentEpithelialEpithelial CellsEpitheliumEventFGFR3 geneFamilyFibroblast Growth FactorFibroblast Growth Factor ReceptorsGastrointestinal tract structureGoalsGrowthGrowth FactorGrowth Factor Receptor GenesIntestinesLiteratureMediatingMediator of activation proteinMenotropinsMolecularMorphogenesisMusMutationNatureNumbersPathway interactionsPeptidesPopulationRateReceptor GeneRoleSignal PathwaySignal TransductionStem cellsTCF7L2 geneTimeTissuesUndifferentiatedbeta catenincell typedaughter cellfibroblast growth factor receptor 3gastrointestinalhydroxymethylglutarateintestinal cryptintestinal epitheliumself-renewalstem cell fatetranscription factor
项目摘要
DESCRIPTION (provided by applicant): Epithelia, such as those lining the gastrointestinal tract, are able to undergo continuous self-renewal because they contain a population of undifferentiated stem cells that have a large capacity for self renewal and can also give rise to daughter cells which are able to differentiate into all of the mature cell types needed for normal function of the epithelial layer. The nature of the signals that mediate the establishment of this hierarchical organization of the epithelium during normal gastrointestinal development has not yet been defined. Fibroblast growth factors (FGFs) are a family of at least 23 related mesenchymally derived peptide growth factors that modulate a wide array of morphogenic and differentiation events occurring during normal ontogeny of a variety of tissues. We have recently found that expression of one FGF receptor gene, FGFR- 3, is restricted to undifferentiated cells in the lower two-thirds of the intestinal crypt epithelium and is maximally expressed during crypt morphogenesis. Additionally, preliminary studies of intestinal development in FGFR3-/- mice, demonstrate that FGFR-3 regulates both the rate of nascent crypt formation and the number of replicating crypt transit cells in the suckling mouse intestine. The central hypothesis of this proposal is that signaling through FGFR-3 regulates the fate and/or proliferation of the multipotent epithelial stem cells during normal intestinal ontogeny. Aim 1 is to determine whether FGFR-3-mediated signaling directly regulates expansion of the epithelial stem cell population during normal intestinal development through effects on stem cell proliferation and/or programmed cell death. Mice with targeted mutations in the FGFR3 receptor gene will be used to determine the effects of FGFR3 mediated signaling on the number of clonogenic stem cells and on apoptosis at various developmental time points. Aim 2 will examine whether the effects of FGFR3 on crypt morphogenesis are mediated through a beta-catenin/TCF-4 dependent mechanism. Evidence in the literature suggests that the HMG transcription factors TCF-4 and Lef-1 are important downstream regulatory mediators of proliferative and apoptotic events in the crypt epithelium. Both cell culture and animal models will be used to determine whether signaling through FGFR3 can modulate TCF-4 activity. The goal of aim 3 is to define the intermediate signaling cascades that FGFR3 uses to regulate morphogenic events during intestinal development. The operant FGFR3 signaling pathways in intestinal epithelial cell lines, especially those impinging on TCF-4, will be investigated using a combination of biochemical and molecular approaches.
描述(由申请人提供):上皮细胞,例如衬在胃肠道的上皮细胞,能够进行连续的自我更新,因为它们含有一群未分化的干细胞,这些干细胞具有很大的自我更新能力,并且还可以产生子细胞,这些子细胞能够分化成上皮层正常功能所需的所有成熟细胞类型。在正常胃肠道发育过程中,介导上皮细胞建立这种分层组织的信号的性质尚未确定。成纤维细胞生长因子(FGF)是至少23种相关的间充质来源的肽生长因子的家族,其调节多种组织的正常个体发育期间发生的多种形态发生和分化事件。我们最近发现,一种FGF受体基因FGFR- 3的表达仅限于下三分之二的肠隐窝上皮中的未分化细胞,并且在隐窝形态发生期间最大程度地表达。此外,FGFR-3-/-小鼠肠道发育的初步研究表明,FGFR-3调节乳鼠肠道中新生隐窝形成的速率和复制隐窝转运细胞的数量。该提议的中心假设是,通过FGFR-3的信号传导调节正常肠个体发育期间多能上皮干细胞的命运和/或增殖。目的1是确定FGFR-3介导的信号传导是否通过对干细胞增殖和/或程序性细胞死亡的影响直接调节正常肠发育期间上皮干细胞群体的扩增。将使用在FGFR 3受体基因中具有靶向突变的小鼠来确定FGFR 3介导的信号传导对克隆发生干细胞的数量和在不同发育时间点对细胞凋亡的影响。目的2将检查FGFR 3对隐窝形态发生的作用是否通过β-连环蛋白/TCF-4依赖性机制介导。文献中的证据表明HMG转录因子TCF-4和Lef-1是隐窝上皮中增殖和凋亡事件的重要下游调节介质。细胞培养和动物模型将用于确定通过FGFR 3的信号传导是否可以调节TCF-4活性。目的3的目标是定义FGFR 3用于调节肠发育期间的形态发生事件的中间信号级联。将使用生物化学和分子方法的组合来研究肠上皮细胞系中的操作性FGFR 3信号传导途径,特别是那些撞击TCF-4的细胞系。
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 }}
STEVEN M COHN其他文献
STEVEN M COHN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('STEVEN M COHN', 18)}}的其他基金
Beta-Defensins: Mediators of Gastrointestinal Inflammation
β-防御素:胃肠道炎症的介质
- 批准号:
7588315 - 财政年份:2009
- 资助金额:
$ 26.68万 - 项目类别:
Beta-Defensins: Mediators of Gastrointestinal Inflammation
β-防御素:胃肠道炎症的介质
- 批准号:
7860381 - 财政年份:2009
- 资助金额:
$ 26.68万 - 项目类别:
Growth Factor Signaling in Intestinal Development
肠道发育中的生长因子信号传导
- 批准号:
7929150 - 财政年份:2009
- 资助金额:
$ 26.68万 - 项目类别:
CORE--Molecular Biology/Gene Expression Core
CORE--分子生物学/基因表达核心
- 批准号:
7447857 - 财政年份:2007
- 资助金额:
$ 26.68万 - 项目类别:
ROLE OF PANETH CELLS AND THEIR DEFENSINS IN THE PATHOGENESIS OF SAMP ILEITIS
潘氏细胞及其防御素在桑普回肠炎发病机制中的作用
- 批准号:
7491473 - 财政年份:2007
- 资助金额:
$ 26.68万 - 项目类别:
ROLE OF PANETH CELLS AND THEIR DEFENSINS IN THE PATHOGENESIS OF SAMP ILEITIS
潘氏细胞及其防御素在桑普回肠炎发病机制中的作用
- 批准号:
7021092 - 财政年份:2005
- 资助金额:
$ 26.68万 - 项目类别:
CORE--Molecular Biology/Gene Expression Core
CORE--分子生物学/基因表达核心
- 批准号:
6797537 - 财政年份:2004
- 资助金额:
$ 26.68万 - 项目类别:
Growth Factor Signaling in Intestinal Development
肠道发育中的生长因子信号传导
- 批准号:
7458851 - 财政年份:2004
- 资助金额:
$ 26.68万 - 项目类别:
Growth Factor Signaling in Intestinal Development
肠道发育中的生长因子信号传导
- 批准号:
7059143 - 财政年份:2004
- 资助金额:
$ 26.68万 - 项目类别:
Growth Factor Signaling in Intestinal Development
肠道发育中的生长因子信号传导
- 批准号:
6822972 - 财政年份:2004
- 资助金额:
$ 26.68万 - 项目类别:
相似国自然基金
Epac1/2通过蛋白酶体调控中性粒细胞NETosis和Apoptosis在急性肺损伤中的作用研究
- 批准号:LBY21H010001
- 批准年份:2020
- 资助金额:0.0 万元
- 项目类别:省市级项目
基于Apoptosis/Ferroptosis双重激活效应的天然产物AlbiziabiosideA的抗肿瘤作用机制研究及其结构改造
- 批准号:81703335
- 批准年份:2017
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
双肝移植后Apoptosis和pyroptosis在移植物萎缩差异中的作用和供受者免疫微环境变化研究
- 批准号:81670594
- 批准年份:2016
- 资助金额:58.0 万元
- 项目类别:面上项目
Serp-2 调控apoptosis和pyroptosis 对肝脏缺血再灌注损伤的保护作用研究
- 批准号:81470791
- 批准年份:2014
- 资助金额:73.0 万元
- 项目类别:面上项目
Apoptosis signal-regulating kinase 1是七氟烷抑制小胶质细胞活化的关键分子靶点?
- 批准号:81301123
- 批准年份:2013
- 资助金额:23.0 万元
- 项目类别:青年科学基金项目
APO-miR(multi-targeting apoptosis-regulatory miRNA)在前列腺癌中的表达和作用
- 批准号:81101529
- 批准年份:2011
- 资助金额:22.0 万元
- 项目类别:青年科学基金项目
放疗与细胞程序性死亡(APOPTOSIS)相关性及其应用研究
- 批准号:39500043
- 批准年份:1995
- 资助金额:9.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Spatial Restriction of Apoptotic Machinery during Neuronal Apoptosis and Pruning
神经元凋亡和修剪过程中凋亡机制的空间限制
- 批准号:
10596657 - 财政年份:2021
- 资助金额:
$ 26.68万 - 项目类别:
Spatial Restriction of Apoptotic Machinery during Neuronal Apoptosis and Pruning
神经元凋亡和修剪过程中凋亡机制的空间限制
- 批准号:
10417219 - 财政年份:2021
- 资助金额:
$ 26.68万 - 项目类别:
Examining the contribution of apoptosis repressor with caspase recruitment domain (ARC) to the anti-apoptotic effect of endurance training in skeletal muscle
检查具有半胱天冬酶募集结构域 (ARC) 的凋亡抑制因子对骨骼肌耐力训练的抗凋亡作用的贡献
- 批准号:
441952-2013 - 财政年份:2015
- 资助金额:
$ 26.68万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Examining the contribution of apoptosis repressor with caspase recruitment domain (ARC) to the anti-apoptotic effect of endurance training in skeletal muscle
检查具有半胱天冬酶募集结构域 (ARC) 的凋亡抑制因子对骨骼肌耐力训练的抗凋亡作用的贡献
- 批准号:
441952-2013 - 财政年份:2014
- 资助金额:
$ 26.68万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Understanding the activation of pro-apoptotic Bcl-2 family proteins for the development of modulators of apoptosis
了解促凋亡 Bcl-2 家族蛋白的激活以开发凋亡调节剂
- 批准号:
nhmrc : 1059331 - 财政年份:2014
- 资助金额:
$ 26.68万 - 项目类别:
Project Grants
Examining the contribution of apoptosis repressor with caspase recruitment domain (ARC) to the anti-apoptotic effect of endurance training in skeletal muscle
检查具有半胱天冬酶募集结构域 (ARC) 的凋亡抑制因子对骨骼肌耐力训练的抗凋亡作用的贡献
- 批准号:
441952-2013 - 财政年份:2013
- 资助金额:
$ 26.68万 - 项目类别:
Postgraduate Scholarships - Doctoral
Apoptotic Osteocytes Promote Chondrocyte Apoptosis via Soluble Factors
凋亡骨细胞通过可溶性因子促进软骨细胞凋亡
- 批准号:
251802 - 财政年份:2012
- 资助金额:
$ 26.68万 - 项目类别:
Studentship Programs
Defining the mechanism(s) by which the cellular inhibitor of apoptosis protein 2 (cIAP2) contributes to early stage atherosclerosis development by directly promoting the participation of key apoptotic pathways within lesion-associated macrophages
确定凋亡蛋白细胞抑制剂 2 (cIAP2) 通过直接促进病变相关巨噬细胞内关键凋亡途径的参与来促进早期动脉粥样硬化发展的机制
- 批准号:
191299 - 财政年份:2009
- 资助金额:
$ 26.68万 - 项目类别:
Operating Grants
ATP release during apoptosis and its relevance to apoptotic cell clearance
凋亡过程中 ATP 释放及其与凋亡细胞清除的相关性
- 批准号:
8075522 - 财政年份:2009
- 资助金额:
$ 26.68万 - 项目类别:
ATP release during apoptosis and its relevance to apoptotic cell clearance
凋亡过程中 ATP 释放及其与凋亡细胞清除的相关性
- 批准号:
7676912 - 财政年份:2009
- 资助金额:
$ 26.68万 - 项目类别: