Molecular basis of digestive system development in Xenopus
Molecular basis of digestive system development in Xenopus
批准号:
9232138
负责人:
Aaron M Zorn
金额:
$33.95万
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-04-01 至 2019-03-31
关键词:
AddressAnimal ModelBindingCellsComplexCongenital AbnormalityDNADNA BindingDataDepositionDevelopmentDigestive System DisordersDiseaseDisease modelElementsEmbryoEmbryonic DevelopmentEndodermEnvironmentExtracellular MatrixFeedbackFelis catusFibronectinsGastrulaGeneticGenetic EpistasisGenetic TranscriptionGoalsGrantGrowth FactorHealthHindgutHomeobox GenesHumanIn VitroIntestinesLiverMammalsMapsMediatingMesodermMetalloproteasesModelingMolecularMorphogenesisNuclearOrganOrganogenesisOutcomeOutputPaperPathway interactionsPatternPeptide HydrolasesPrimitive foregut structureProteinsPublishingRegulationRegulatory ElementReplacement TherapyResearchRoleSeriesSignal TransductionSpecific qualifier valueSpecificityStem cellsSystems DevelopmentTestingTimeTissuesWNT Signaling PathwayXenopusbeta catenincombinatorialextracellulargastrointestinal systemgastrulationheparin proteoglycanhuman stem cellsmalformationnovelprogenitorpromoterpublic health relevanceresponsesegregationstem cell differentiationsyndecan-4
中文摘要
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英文摘要
DESCRIPTION (provided by applicant): The long-term goal of this project is to elucidate the molecular mechanisms controlling embryonic development of the digestive system. This will have a broad and significant impact on our understanding of human GI malformations, inform strategies to direct the differentiation of stem cells and provide new fundamental information on cell signaling in development and disease. Digestive system development is regulated by a series of growth factor signals between the endoderm and mesoderm, which are only partially understood. The fundamental mechanism of GI development are highly conserved between mammals and other vertebrate species and our previous studies using the experimental advantages of Xenopus embryos has helped inform strategies to induce human intestinal tissue from stem cells. Despite recent advances, fundamental gaps in our understanding of how foregut and hindgut progenitors are specified remain. In particular how the extracellular environment regulates combinatorial signaling dynamics at different stages of GI development, and how transcriptional specificity in response to these signal is achieved are largely unknown and the focus of this proposal. Our preliminary studies support the hypothesis that Secreted Frizzed Related Proteins (Sfrp) regulate the extracellular Fibronectin matrix to promote BMP signaling by a novel mechanism, and that Sfrps coordinate signaling crosstalk between BMP and Wnt growth factors to pattern the endoderm into foregut and hindgut progenitors. Aim 1 will characterize the novel mechanisms by which Sfrps and Tolloid proteases modulate the Fibronectin matrix to regulate BMP signaling. Aim 2 will determine the mechanisms that coordinate BMP and Wnt signaling. Aim 3 will determine how differential activity of the BMP and Wnt signaling effectors Smad1 and beta-catenin are integrated on DNA cis-regulatory elements to control foregut versus hindgut transcription.
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Modeling human development and disease in Xenopus. Preface.
在非洲爪蟾中模拟人类发育和疾病。
DOI:
10.1016/j.ydbio.2015.11.019
发表时间:
2015
期刊:
Developmental biology
影响因子:
2.7
作者:
[LaBonne,Carole, Zorn,AaronM]
通讯作者:
Zorn,AaronM
DOI:
10.1016/j.celrep.2016.05.060
发表时间:
2016-06-28
期刊:
Cell reports
影响因子:
8.8
作者:
[Rankin SA, Han L, McCracken KW, Kenny AP, Anglin CT, Grigg EA, Crawford CM, Wells JM, Shannon JM, Zorn AM]
通讯作者:
Zorn AM
Syndecan4 coordinates Wnt/JNK and BMP signaling to regulate foregut progenitor development.
Syndecan4 协调 Wnt/JNK 和 BMP 信号传导以调节前肠祖细胞发育。
DOI:
10.1016/j.ydbio.2016.05.025
发表时间:
2016
期刊:
Developmental biology
影响因子:
2.7
作者:
[Zhang,Zheng, Rankin,ScottA, Zorn,AaronM]
通讯作者:
Zorn,AaronM
DOI:
10.1016/j.jmb.2012.10.003
发表时间:
2012-12-14
期刊:
JOURNAL OF MOLECULAR BIOLOGY
影响因子:
5.6
作者:
[Kattamuri, Chandramohan, Luedeke, David M., Nolan, Kristof, Rankin, Scott A., Greis, Kenneth D., Zorn, Aaron M., Thompson, Thomas B.]
通讯作者:
Thompson, Thomas B.
Different thresholds of Wnt-Frizzled 7 signaling coordinate proliferation, morphogenesis and fate of endoderm progenitor cells.
Wnt-Frizz的不同阈值7信号传导坐标坐标增殖,形态发生和内胚层祖细胞的命运。
DOI:
10.1016/j.ydbio.2013.02.024
发表时间:
2013-06-01
期刊:
DEVELOPMENTAL BIOLOGY
影响因子:
2.7
作者:
[Zhang, Zheng, Rankin, Scott A., Zorn, Aaron M.]
通讯作者:
Zorn, Aaron M.
Sox Proteins Modulate Genomic Specificity of B-catenin Regulated Transcription in the Developing Gut
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批准号:10540791
-
项目类别:
-
资助金额:$55.71万
-
财政年份:2021
-
负责人:Aaron M Zorn
-
依托单位:
Sox Proteins Modulate Genomic Specificity of B-catenin Regulated Transcription in the Developing Gut
-
批准号:10115171
-
项目类别:
-
资助金额:$55.71万
-
财政年份:2021
-
负责人:Aaron M Zorn
-
依托单位:
Sox Proteins Modulate Genomic Specificity of B-catenin Regulated Transcription in the Developing Gut
-
批准号:10328965
-
项目类别:
-
资助金额:$55.71万
-
财政年份:2021
-
负责人:Aaron M Zorn
-
依托单位:
Modeling the molecular and cellular mechanisms of TE birth defects in animals
-
批准号:10174985
-
项目类别:
-
资助金额:$32.4万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Admin Core
-
批准号:10647823
-
项目类别:
-
资助金额:$7.95万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Admin Core
-
批准号:10458158
-
项目类别:
-
资助金额:$7.95万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Project-2: Modeling TE birth defects in animals
-
批准号:10647834
-
项目类别:
-
资助金额:$40.08万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Developmental Mechanisms of Trachea-Esophageal Birth Defects
-
批准号:10174982
-
项目类别:
-
资助金额:$6.07万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Developmental Mechanisms of Trachea-Esophageal Birth Defects
-
批准号:10174983
-
项目类别:
-
资助金额:$12.82万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Project-2: Modeling TE birth defects in animals
-
批准号:10458161
-
项目类别:
-
资助金额:$40.89万
-
财政年份:2017
-
负责人:Aaron M Zorn
-
依托单位:
Osr transcription factors regulate embryonic lung development
-
批准号:8343489
-
项目类别:
-
资助金额:$38.25万
-
财政年份:2012
-
负责人:Aaron M Zorn
-
依托单位:
Osr transcription factors regulate embryonic lung development
-
批准号:8526545
-
项目类别:
-
资助金额:$36.41万
-
财政年份:2012
-
负责人:Aaron M Zorn
-
依托单位:
Osr transcription factors regulate embryonic lung development
-
批准号:8693648
-
项目类别:
-
资助金额:$37.49万
-
财政年份:2012
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Dissemination
-
批准号:10674816
-
项目类别:
-
资助金额:$13.37万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Curation
-
批准号:10674806
-
项目类别:
-
资助金额:$71.38万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Curation
-
批准号:10404999
-
项目类别:
-
资助金额:$70.37万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Admin Core
-
批准号:10404998
-
项目类别:
-
资助金额:$6.46万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Tech Development
-
批准号:10674810
-
项目类别:
-
资助金额:$23.38万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Admin Core
-
批准号:10674804
-
项目类别:
-
资助金额:$7.47万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
Xenbase - Computation
-
批准号:10405001
-
项目类别:
-
资助金额:$48.07万
-
财政年份:2010
-
负责人:Aaron M Zorn
-
依托单位:
海外基金