Molecular mechanisms of PITX2 during craniofacial development

PITX2在颅面发育过程中的分子机制

基本信息

  • 批准号:
    8528389
  • 负责人:
  • 金额:
    $ 35.52万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2012
  • 资助国家:
    美国
  • 起止时间:
    2012-10-01 至 2015-02-28
  • 项目状态:
    已结题

项目摘要

In recent years a number of new genes have been identified that are involved in tooth morphogenesis. Though much progress has been made in identifying new genes and the signaling mechanisms that regulate morphogenetic stages of tooth development have been documented, the transcriptional mechanisms that regulate proliferation and differentiation of the odontoblasts and ameloblasts are poorly understood. Better understanding of the mechanistic aspect of this process is necessary, not only to understand normal tooth morphogenesis, but also to regenerate teeth, and eventually be able to develop and deliver better therapeutic strategies. PITX2 provides a unique tool for studying the molecular control of tooth formation since it is selectively expressed at the earliest stage of tooth development. We have only begun to understand the molecular mechanisms of PITX2, its role in tooth development and the downstream hierarchy of transcription factors involved in craniofacial/tooth development. The focus of this continuing grant application is to understand the molecular mechanisms by which PITX2 interacts with other factors to regulate tooth development. Our previous results demonstrate that PITX2 acts in concert with other factors to regulate gene expression. We propose to test our hypothesis that PITX2 differentially regulates gene expression through specific protein-protein interactions with T-box factors Tbx1 and Tbx18 and the LIM homeodomain factors Islet-1 and Lhx6. HMG-17, a chromatin associated factor recruits PITX2 to active chromatin and is activated through Wnt/-catenin signaling. We will test our hypothesis that the transcriptional activity of PITX2 is tightly regulated during development by its interaction with HMG-17, -catenin, acetylated histones and chromatin remodeling factors. MicroRNAs (miR's) are critical to controlling gene expression however little is known about their role in craniofacial/tooth development. Preliminary data demonstrates that miR's directly control the patterning of incisors and molars, specifying a combinatorial code of miR expression for normal craniofacial/tooth development. We will test our hypothesis that specific miR's expressed during tooth development control the activities of specific transcription factors and the patterning of teeth. Understanding how these components interact to promote normal craniofacial development will further our understanding of genetic defects.
近年来,已经发现了一些与牙齿有关的新基因

项目成果

期刊论文数量(23)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dact2 represses PITX2 transcriptional activation and cell proliferation through Wnt/beta-catenin signaling during odontogenesis.
  • DOI:
    10.1371/journal.pone.0054868
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Li X;Florez S;Wang J;Cao H;Amendt BA
  • 通讯作者:
    Amendt BA
MicroRNA-26b represses colon cancer cell proliferation by inhibiting lymphoid enhancer factor 1 expression.
  • DOI:
    10.1158/1535-7163.mct-13-1000
  • 发表时间:
    2014-07
  • 期刊:
  • 影响因子:
    5.7
  • 作者:
    Zhang Z;Kim K;Li X;Moreno M;Sharp T;Goodheart MJ;Safe S;Dupuy AJ;Amendt BA
  • 通讯作者:
    Amendt BA
Tbx1 regulates progenitor cell proliferation in the dental epithelium by modulating Pitx2 activation of p21.
  • DOI:
    10.1016/j.ydbio.2010.08.031
  • 发表时间:
    2010-11-15
  • 期刊:
  • 影响因子:
    2.7
  • 作者:
    Cao H;Florez S;Amen M;Huynh T;Skobe Z;Baldini A;Amendt BA
  • 通讯作者:
    Amendt BA
MicroRNAs play a critical role in tooth development.
  • DOI:
    10.1177/0022034510369304
  • 发表时间:
    2010-08
  • 期刊:
  • 影响因子:
    7.6
  • 作者:
    Cao H;Wang J;Li X;Florez S;Huang Z;Venugopalan SR;Elangovan S;Skobe Z;Margolis HC;Martin JF;Amendt BA
  • 通讯作者:
    Amendt BA
Fuz regulates craniofacial development through tissue specific responses to signaling factors.
  • DOI:
    10.1371/journal.pone.0024608
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Zhang Z;Wlodarczyk BJ;Niederreither K;Venugopalan S;Florez S;Finnell RH;Amendt BA
  • 通讯作者:
    Amendt BA
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BRAD A AMENDT其他文献

BRAD A AMENDT的其他文献

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{{ truncateString('BRAD A AMENDT', 18)}}的其他基金

Co-opting Lef-1 and miR-26b activities to regulate dental stem cells and their progeny
共同选择 Lef-1 和 miR-26b 活性来调节牙齿干细胞及其后代
  • 批准号:
    10664967
  • 财政年份:
    2020
  • 资助金额:
    $ 35.52万
  • 项目类别:
Co-opting Lef-1 and miR-26b activities to regulate dental stem cells and their progeny
共同选择 Lef-1 和 miR-26b 活性来调节牙齿干细胞及其后代
  • 批准号:
    10453572
  • 财政年份:
    2020
  • 资助金额:
    $ 35.52万
  • 项目类别:
Co-opting Lef-1 and miR-26b activities to regulate dental stem cells and their progeny
共同选择 Lef-1 和 miR-26b 活性来调节牙齿干细胞及其后代
  • 批准号:
    9885121
  • 财政年份:
    2020
  • 资助金额:
    $ 35.52万
  • 项目类别:
Co-opting Lef-1 and miR-26b activities to regulate dental stem cells and their progeny
共同选择 Lef-1 和 miR-26b 活性来调节牙齿干细胞及其后代
  • 批准号:
    10219232
  • 财政年份:
    2020
  • 资助金额:
    $ 35.52万
  • 项目类别:
Oral and Craniofacial Bone Regeneration using MicroRNA Modulation
使用 MicroRNA 调制进行口腔和颅面骨再生
  • 批准号:
    10192700
  • 财政年份:
    2017
  • 资助金额:
    $ 35.52万
  • 项目类别:
University of Iowa Institutional Training Program in Oral Health Research
爱荷华大学口腔健康研究机构培训计划
  • 批准号:
    10434702
  • 财政年份:
    2013
  • 资助金额:
    $ 35.52万
  • 项目类别:
University of Iowa Institutional Training Program in Oral Health Research
爱荷华大学口腔健康研究机构培训计划
  • 批准号:
    10434814
  • 财政年份:
    2013
  • 资助金额:
    $ 35.52万
  • 项目类别:
University of Iowa Institutional Training Program in Oral Health Research
爱荷华大学口腔健康研究机构培训计划
  • 批准号:
    10201565
  • 财政年份:
    2013
  • 资助金额:
    $ 35.52万
  • 项目类别:
University of Iowa Institutional Training Program in Oral Health Research
爱荷华大学口腔健康研究机构培训计划
  • 批准号:
    10201567
  • 财政年份:
    2013
  • 资助金额:
    $ 35.52万
  • 项目类别:
Molecular mechanisms of PITX2 during craniofacial development
PITX2在颅面发育过程中的分子机制
  • 批准号:
    8550273
  • 财政年份:
    2012
  • 资助金额:
    $ 35.52万
  • 项目类别:
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