Signals and mechanical forces controlling radial gut morphogenesis
控制径向肠道形态发生的信号和机械力
基本信息
- 批准号:10442794
- 负责人:
- 金额:$ 35.02万
- 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:2016-04-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAgonistAnatomyArchitectureBiochemicalBiophysicsCharacteristicsChickChick EmbryoComputer ModelsCongenital AbnormalityDefectDevelopmentDimensionsEmbryonic DevelopmentEnvironmentEpithelialEquilibriumErinaceidaeEsophagusEventFamilyFiberFingersGastrocoeleGastrointestinal tract structureGene Expression ProfilingGenerationsGenesGenetic TranscriptionGrowthHindgutIn Situ HybridizationLarge IntestineLeadLightLinkLocationMeasuresMechanicsMesenchymeMesodermMicrodissectionMidgutMolecularMolecular GeneticsMorphogenesisMorphologyMucous MembraneMuscleMuscle FibersNutrientOrganPathway interactionsPatternPharmaceutical PreparationsPlayPrimatesPrimitive foregut structurePropertyRadialRetroviral VectorRoleSeriesShapesSignal InductionSignal TransductionSmall IntestinesSmooth MuscleSpecific qualifier valueStressStructureSurfaceSystemTestingThickTimeTissue RecombinationTissuesTo specifyTubeUndifferentiatedVariantVillusWorkantagonistbiophysical propertiesexperienceexperimental studygastrointestinal epitheliumin vivoinsightintestinal villimathematical modelmechanical forcemorphogensprogramstranscription factortranscription factor USF
项目摘要
PROJECT SUMMARY/ABSTRACT
The midgut is characterized by a series of concentric, mesodermally-derived layers of smooth muscle
and mucosa, surrounding an inner, endodermally-derived epithelium. In the mature gut, this epithelium forms
finger-like projections extending into the lumen, called villi. In the developing chick, intestinal villi are generated
in a step-wise manner, through a series of epithelial buckling events. Buckling forces are generated through
the confined growth of the epithelium at a time when expansion is restricted by the adjacent differentiating
smooth muscle. The physical constraint experienced by the epithelium changes over time as different layers of
smooth muscle are established sequentially. The location of these smooth muscle layers is established
through the activity of gradients of Shh and Bmp, which, respectively, have positive and negative effects on
smooth muscle differentiation. As they form, the orientation of the fibers in each muscle layer depends upon
the mechanical environment of the gut at the time the layer undergoes differentiation. In spite of this general
outline of how the midgut architecture is established, there is a dearth of information regarding the tissue-level
construction of the other gut segments. Both the foregut and the hindgut arise from the same linear primative
gut tube as the midgut, and have the same general concentric organization. However, there are significant
differences in the thickness and timing of smooth muscle differentiation in the different gut segments, and the
epithelial lining differs dramatically in the three segments. In Aim 1, the mechanisms responsible for the distinct
characteristics of the muscle layers in the fore- and hindgut will be elucidated. The signaling systems known to
be responsible for defining the location and thickness of the smooth muscle in the midgut will be examined in
the fore- and hindgut segments qualitatively (by in situ hybridization) as well as quantitatively (by qPCR) to
determine how they differ in expression from the midgut. These signals will be manipulated by electoration in
vivo and through culturing with agonists and antagonists in explant culture and utilizing tissue recombination to
test their roles functionally. Experiments in Aim 2 will determine the extent to which these differences in smooth
muscle architecture and dynamics are responsible for the distinct epithelial morphology of the fore-and hind
guts. Drugs will be employed to block smooth muscle differentiation to test their necessity. Morphometric and
biophysical parameters will be measured and entered into computational models to test the degree to which
epithelial morphology can be entirely explained on this basis. Finally, in Aim 3 we will assess how transcription
factors of the Hox and paraHox clusters, known to specify regional identity within the gut, alter the molecular
and physical parameters that differentiate the fore-, mid- and hindgut, thereby connecting regional patterning to
morphogenesis of the gut. To that end, transcription fctors involved in regional identity will be misexpressed
ustilizing retroviral vectors, and changes in biochemical and mechanical parameters will be examined.
项目概要/摘要
中肠的特征是一系列同心、中胚层衍生的平滑肌层
和粘膜,围绕内胚层衍生的上皮。在成熟的肠道中,这种上皮形成
伸入管腔的手指状突起,称为绒毛。在发育中的雏鸡中,产生肠绒毛
以逐步的方式,通过一系列上皮屈曲事件。屈曲力是通过产生的
当扩张受到邻近分化的限制时,上皮的有限生长
平滑肌。上皮所经历的物理约束随着时间的推移而变化,因为不同的层
平滑肌依次建立。这些平滑肌层的位置已确定
通过Shh和Bmp梯度的活动,它们分别对
平滑肌分化。当它们形成时,每个肌肉层中纤维的方向取决于
该层进行分化时肠道的机械环境。尽管有这样的一般
关于中肠结构如何建立的概述,缺乏有关组织水平的信息
其他肠道片段的构建。前肠和后肠都源自同一个线性原语
肠管如同中肠,一般具有相同的同心组织。然而,有显着
不同肠段平滑肌分化的厚度和时间存在差异,
这三个部分的上皮衬里差异很大。在目标 1 中,负责不同的机制
将阐明前肠和后肠肌肉层的特征。已知的信号系统
负责定义中肠平滑肌的位置和厚度将在以下中进行检查
定性(通过原位杂交)和定量(通过 qPCR)对前肠和后肠片段进行分析
确定它们与中肠的表达有何不同。这些信号将受到选举的操纵
体内并通过在外植体培养物中与激动剂和拮抗剂一起培养并利用组织重组来
测试他们的角色功能。目标 2 中的实验将确定这些平滑差异的程度
肌肉结构和动力学决定了前后肢不同的上皮形态
胆量。将使用药物来阻止平滑肌分化以测试其必要性。形态测量和
将测量生物物理参数并将其输入计算模型以测试其程度
在此基础上可以完全解释上皮形态。最后,在目标 3 中,我们将评估转录如何
Hox 和 paraHox 簇的因子已知可指定肠道内的区域特征,从而改变分子
以及区分前肠、中肠和后肠的物理参数,从而将区域模式与
肠道的形态发生。为此,涉及区域身份的转录因子将被错误表达
利用逆转录病毒载体,并检查生化和机械参数的变化。
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 }}
CLIFFORD J. TABIN其他文献
CLIFFORD J. TABIN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('CLIFFORD J. TABIN', 18)}}的其他基金
Signals and mechanical forces controlling radial gut morphogenesis
控制径向肠道形态发生的信号和机械力
- 批准号:
10684660 - 财政年份:2016
- 资助金额:
$ 35.02万 - 项目类别:
Integrating Forces and Signals in Tissue-Level Patterning of the Developing Digestive Tract
将力和信号整合到发育中消化道的组织水平模式中
- 批准号:
9244822 - 财政年份:2016
- 资助金额:
$ 35.02万 - 项目类别:
A genetic system for the study of vertebrate limb regeneration
用于研究脊椎动物肢体再生的遗传系统
- 批准号:
8121590 - 财政年份:2010
- 资助金额:
$ 35.02万 - 项目类别:
A genetic system for the study of vertebrate limb regeneration
用于研究脊椎动物肢体再生的遗传系统
- 批准号:
7963530 - 财政年份:2010
- 资助金额:
$ 35.02万 - 项目类别:
The Roles of BMP Genes and Morphogenesis of the Appendicular and Dermal Skeletons
BMP 基因的作用以及阑尾和真皮骨骼的形态发生
- 批准号:
7432430 - 财政年份:2007
- 资助金额:
$ 35.02万 - 项目类别:
Lineage and cell migration in patterning the limb primordium
肢体原基模式中的谱系和细胞迁移
- 批准号:
8460894 - 财政年份:2005
- 资助金额:
$ 35.02万 - 项目类别:
Lineage and cell migration in patterning the limb primordium
肢体原基模式中的谱系和细胞迁移
- 批准号:
8291903 - 财政年份:2005
- 资助金额:
$ 35.02万 - 项目类别:
Lineage and cell migration in patterning the limb primordium
肢体原基模式中的谱系和细胞迁移
- 批准号:
8680266 - 财政年份:2005
- 资助金额:
$ 35.02万 - 项目类别:
相似国自然基金
Agonist-GPR119-Gs复合物的结构生物学研究
- 批准号:32000851
- 批准年份:2020
- 资助金额:24.0 万元
- 项目类别:青年科学基金项目
相似海外基金
S1PR1 agonistによる脳血液関門制御を介した脳梗塞の新規治療法開発
S1PR1激动剂调节血脑屏障治疗脑梗塞新方法的开发
- 批准号:
24K12256 - 财政年份:2024
- 资助金额:
$ 35.02万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
AHR agonistによるSLE皮疹の新たな治療薬の開発
使用 AHR 激动剂开发治疗 SLE 皮疹的新疗法
- 批准号:
24K19176 - 财政年份:2024
- 资助金额:
$ 35.02万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Evaluation of a specific LXR/PPAR agonist for treatment of Alzheimer's disease
特定 LXR/PPAR 激动剂治疗阿尔茨海默病的评估
- 批准号:
10578068 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
AUGMENTING THE QUALITY AND DURATION OF THE IMMUNE RESPONSE WITH A NOVEL TLR2 AGONIST-ALUMINUM COMBINATION ADJUVANT
使用新型 TLR2 激动剂-铝组合佐剂增强免疫反应的质量和持续时间
- 批准号:
10933287 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
Targeting breast cancer microenvironment with small molecule agonist of relaxin receptor
用松弛素受体小分子激动剂靶向乳腺癌微环境
- 批准号:
10650593 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
AMPKa agonist in attenuating CPT1A inhibition and alcoholic chronic pancreatitis
AMPKa 激动剂减轻 CPT1A 抑制和酒精性慢性胰腺炎
- 批准号:
10649275 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
A randomized double-blind placebo controlled Phase 1 SAD study in male and female healthy volunteers to assess safety, pharmacokinetics, and transient biomarker changes by the ABCA1 agonist CS6253
在男性和女性健康志愿者中进行的一项随机双盲安慰剂对照 1 期 SAD 研究,旨在评估 ABCA1 激动剂 CS6253 的安全性、药代动力学和短暂生物标志物变化
- 批准号:
10734158 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation
研究阿片类激动剂治疗 OUD 患者结果的机制:解开睡眠和昼夜节律对渴望和情绪调节的影响
- 批准号:
10784209 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
A novel nanobody-based agonist-redirected checkpoint (ARC) molecule, aPD1-Fc-OX40L, for cancer immunotherapy
一种基于纳米抗体的新型激动剂重定向检查点 (ARC) 分子 aPD1-Fc-OX40L,用于癌症免疫治疗
- 批准号:
10580259 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
Identification and characterization of a plant growth promoter from wild plants: is this a novel plant hormone agonist?
野生植物中植物生长促进剂的鉴定和表征:这是一种新型植物激素激动剂吗?
- 批准号:
23K05057 - 财政年份:2023
- 资助金额:
$ 35.02万 - 项目类别:
Grant-in-Aid for Scientific Research (C)














{{item.name}}会员




