The roles of Inturned in mammalian lung development
The roles of Inturned in mammalian lung development
批准号:
10380773
负责人:
AIMIN LIU
金额:
$8.03万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-04-05 至 2024-03-31
关键词:
AffectApoptosisBiochemicalBiological AssayBirthCandidate Disease GeneCellsCellular biologyCiliaCongenital AbnormalityDefectDevelopmentDistalEarly InterventionEmbryoErinaceidaeExhibitsFamilyGene Expression ProfileGene Expression ProfilingGenesGeneticGenetic TranscriptionGrowthIn Situ HybridizationInterventionLeadLeftLungLung diseasesMethodsMolecularMorphogenesisMusMutationNeural tubeOutputPathway interactionsPatternPlatelet-Derived Growth FactorPlayPreventionProteinsRNAResearchReverse Transcriptase Polymerase Chain ReactionRoleSHH geneSeriesSignal PathwaySignal TransductionSignaling MoleculeSkeletal DevelopmentStructure of parenchyma of lungTestingTimeTissuescilium biogenesisdifferential expressionin vivoinsightlung developmentmalformationmembermutantpreventive interventionrare conditionresponsesmoothened signaling pathwaytranscription factortranscriptometranscriptomics
中文摘要
项目摘要
先天性肺畸形(CLM)是一系列罕见的出生缺陷,在最严重的情况下,出生时就会致命。
要有效预防和及早干预这些缺陷,需要全面了解这些缺陷的机制
以胚胎肺的形态发生为基础。PI发现小鼠胚胎突变为CPLANE(纤毛
和平面极性效应器)蛋白在胚胎的生长和呼吸道分支中表现出严重的缺陷
肺部。PI将检验这样的假设,即Intu的丢失会导致纤毛形成的严重丧失,从而损害纤毛-
依赖于HH和PDGF信号。他将研究体内INTU的缺失是否会影响HH和PDGF途径的输出
培养条件下肺组织对Shh和PDGF的反应。他还将测试Intu和A之间的基因交互作用
HH途径的关键调节因子Gli2在肺形态发生中的作用。随后,他将研究Intu突变对
通过候选基因方法在胚胎肺发育中的信号通路和组织模式,其中
已知的肺发育调节因子将被检查。他随后将研究Intu突变是否改变了
肺发育中的增殖和程序性细胞死亡。最后,PI将采取转录转录方法,以
比较野生型和Intu突变肺的转录图谱。拟议的研究将揭示这些角色
研究CPLANE蛋白和纤毛在胚胎肺发育中的作用,有助于更好地了解肺部疾病
例如CLM。
英文摘要
Project Summary
Congenital Lung Malformation (CLM) is a series of rare birth defects that in the most severe case are fatal at birth.
The effective prevention and early intervention of these defects require a comprehensive understanding of the mechanisms
underlying the morphogenesis of the embryonic lungs. The PI found that mouse embryos mutant for the CPLANE (cilia
and planar polarity effector) protein Intu exhibited severe defects in the growth and airway branching of the embryonic
lungs. The PI will test the hypothesis that loss of Intu leads to severe loss of cilia formation, hence compromised cilia-
dependent Hh and PDGF signaling. He will examine whether loss of Intu affects Hh and PDGF pathway outputs in vivo
and the response of the lung tissue to Shh and PDGF in culture. He will also test the genetic interaction between Intu and a
key regulator of Hh pathway, Gli2, in lung morphogenesis. Subsequently, He will examine the impact of Intu mutation on
signaling pathways and tissue patterning in embryonic lung development through a candidate gene approach, in which
known regulators of lung development will be examined. He will subsequently examine whether Intu mutation alters the
proliferation and programmed cell death in lung development. Finally, the PI will take a transcriptomics approach, to
compare the transcriptional profiles between wild type and Intu mutant lungs. The proposed research will reveal the roles
of CPLANE proteins and cilia in embryonic lung development, and contribute to the better understanding of lung diseases
such as CLM.
期刊论文(1)
专著(0)
科研奖励(0)
会议论文
DOI:
10.1016/j.gep.2022.119257
发表时间:
2022-09
期刊:
GENE EXPRESSION PATTERNS
影响因子:
1.2
作者:
[Wang, Yuan, Herzig, Graham, Molano, Cassandra, Liu, Aimin]
通讯作者:
Liu, Aimin
The roles of Inturned in mammalian lung development
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批准号:10216780
-
项目类别:
-
资助金额:$8.03万
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财政年份:2021
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负责人:AIMIN LIU
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依托单位:
Analysis of Flexo/lft88, a novel regulator of Hh pathway
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批准号:6943369
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项目类别:
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财政年份:2004
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依托单位:
Analysis of Flexo/lft88, a novel regulator of Hh pathway
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批准号:6877042
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项目类别:
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资助金额:$4.38万
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财政年份:2004
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负责人:AIMIN LIU
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依托单位:
Analysis of Flexo/lft88, a novel regulator of Hh pathway
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批准号:6791716
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项目类别:
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资助金额:$1.92万
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财政年份:2004
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负责人:AIMIN LIU
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依托单位:
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