Genetic Regulatory Network in Craniofacial Development

颅面发育中的遗传调控网络

基本信息

  • 批准号:
    10337244
  • 负责人:
  • 金额:
    $ 66.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-07-01 至 2024-01-31
  • 项目状态:
    已结题

项目摘要

Title Genetic Regulatory Network in Craniofacial Development Abstract This proposal continues our efforts to decipher the skeletogenic signaling network underlying craniofacial development and disease. The craniofacial skeleton consists of viscerocranium and neurocranium, which is subdivided into the calvarium and chondrocranium. During development of the calvarium, cranial sutures serve as the growth center for skeletogenesis. Defects in suture morphogenesis resulting in premature closure cause craniosynostosis, a devastating childhood disease affecting 1 in ~2,500 individuals. Although human genetic analyses have identified genes associated with the pathogenesis, little is known about the regulation of suture closure essential for development of a healthy skull. In the previously proposed investigation, we have elucidated the mechanisms by which Axin2 regulates suture morphogenesis through modulations of Wnt and downstream signaling pathways. The crosstalk of BMP and FGF signaling plays a pivotal role in Wnt-mediated craniofacial bone development. Furthermore, skeletal stem cells residing in the suture mesenchyme have been successfully identified and isolated in our laboratory. This suture stem cell (SuSC) population is responsible for calvarial development in infants as well as homeostatic maintenance in adults. Upon injury, the dormant SuSCs respond quickly and contribute directly to bone repair in a cell autonomous fashion. In vivo clonal analysis demonstrates calvarial bone regeneration at a single cell level. Implantation of SuSCs to an injured site shows not only long-term survival but also facilitation of bone healing via direct engraftments in which the implanted stem cells give rise to osteogenic cell types in replacement of the damaged tissue. The newly discovered SuSCs thus provides an outstanding opportunity to gain novel insights into etiology of craniosynostosis. In this proposal, we continue our in-depth evaluations of SuSCs by examining their regulation essential for healthy development and homeostasis of the calvarium. We will concentrate on elucidation of molecular and cellular mechanisms underlying craniosynostosis caused by dysregulation of SuSCs.
标题 颅面发育的遗传调控网络 摘要 这项提议继续我们的努力,破译颅面下的骨骼信号网络。 发展和疾病。颅面骨架由内脏颅骨和脑颅骨组成, 又分为头盖骨和软骨头骨。在颅骨发育过程中,颅缝用于 作为骨骼形成的生长中心。缝线形态发生缺陷导致过早闭合 颅缝早闭,一种破坏性的儿童疾病,每2,500人中就有1人患病。虽然人类基因 分析已经确定了与发病机制相关的基因,对缝合的调节知之甚少。 闭合对于发育一个健康的头骨是必不可少的。在之前提出的调查中,我们有 阐明Axin2通过调节Wnt和Wnt调控缝线形态发生的机制 下游信号通路。骨形态发生蛋白和成纤维细胞生长因子信号的串扰在Wnt介导中起着关键作用 头面部骨骼发育。此外,存在于缝合间充质中的骨骼干细胞已经被 在我们实验室成功鉴定和分离。这种缝合干细胞(SuSC)群体负责 婴儿的头盖骨发育以及成人的动态平衡维持。一旦受伤,休眠的人 SuSCs反应迅速,以细胞自主的方式直接促进骨修复。体内克隆 分析表明,颅骨再生在单细胞水平上。自体骨髓间充质干细胞移植于创伤患者 Site不仅显示了长期存活,而且通过直接植入促进了骨愈合,其中 移植的干细胞会产生不同类型的成骨细胞来替代受损的组织。最新的 因此,发现的SuSCs提供了一个绝佳的机会,以获得对疾病病因的新见解。 颅骨融合症。在本提案中,我们继续对SuSC进行深入评估,方法是检查其 对头盖骨的健康发育和动态平衡至关重要的调节。我们将专注于 基因异常引起的颅缝早闭的分子和细胞机制 SuSCs。

项目成果

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Wei Hsu其他文献

Wei Hsu的其他文献

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{{ truncateString('Wei Hsu', 18)}}的其他基金

Nonclassical β-catenin signaling in odontogenesis
牙发生中的非经典β-连环蛋白信号传导
  • 批准号:
    10714280
  • 财政年份:
    2023
  • 资助金额:
    $ 66.21万
  • 项目类别:
Genetic Regulatory Network in Craniofacial Development
颅面发育中的遗传调控网络
  • 批准号:
    10547798
  • 财政年份:
    2021
  • 资助金额:
    $ 66.21万
  • 项目类别:
Genetic Regulatory Network in Craniofacial Development
颅面发育中的遗传调控网络
  • 批准号:
    10440858
  • 财政年份:
    2021
  • 资助金额:
    $ 66.21万
  • 项目类别:
Stem cells for craniofacial bone repair and regeneration
用于颅面骨修复和再生的干细胞
  • 批准号:
    10440848
  • 财政年份:
    2021
  • 资助金额:
    $ 66.21万
  • 项目类别:
Stem cells for craniofacial bone repair and regeneration
用于颅面骨修复和再生的干细胞
  • 批准号:
    10473883
  • 财政年份:
    2021
  • 资助金额:
    $ 66.21万
  • 项目类别:
Stem cells for craniofacial bone repair and regeneration
用于颅面骨修复和再生的干细胞
  • 批准号:
    9927910
  • 财政年份:
    2018
  • 资助金额:
    $ 66.21万
  • 项目类别:
Genetic Regulatory Network in Craniofacial Development
颅面发育中的遗传调控网络
  • 批准号:
    8667323
  • 财政年份:
    2006
  • 资助金额:
    $ 66.21万
  • 项目类别:
GENETIC REGULATORY NETWORK IN CRANIOFACIAL DEVELOPMENT
颅面发育中的遗传调控网络
  • 批准号:
    7835696
  • 财政年份:
    2006
  • 资助金额:
    $ 66.21万
  • 项目类别:
GENETIC REGULATORY NETWORK IN CRANIOFACIAL DEVELOPMENT
颅面发育中的遗传调控网络
  • 批准号:
    7626374
  • 财政年份:
    2006
  • 资助金额:
    $ 66.21万
  • 项目类别:
Genetic Regulatory Network in Craniofacial Development
颅面发育中的遗传调控网络
  • 批准号:
    8481531
  • 财政年份:
    2006
  • 资助金额:
    $ 66.21万
  • 项目类别:

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