Probing Bone Morphogenetic Protein function in Cranial Neural Crest cells.

探索颅神经嵴细胞中的骨形态发生蛋白功能。

基本信息

  • 批准号:
    RGPIN-2015-06006
  • 负责人:
  • 金额:
    $ 2.48万
  • 依托单位:
  • 依托单位国家:
    加拿大
  • 项目类别:
    Discovery Grants Program - Individual
  • 财政年份:
    2016
  • 资助国家:
    加拿大
  • 起止时间:
    2016-01-01 至 2017-12-31
  • 项目状态:
    已结题

项目摘要

Probing Bone Morphogenetic Protein function in Cranial Neural Crest cells The orofacial region is most complex. It comes in a wide variety of shapes and is home to several highly specialized structures. Central to its development are cranial neural crest cells (CNC). During embryonic development CNC cells migrate from the neural plate border to the branchial arches from which the facial prominences and different tissues are formed. CNC cells are multipotent stem cells that give rise to bone, cartilage, nerves, teeth, glial cells, melanocytes, and connective tissue of the face. The signals controlling their migration, differentiation, and proliferation are still only partly understood, though the importance of only a handful of extracellular signalling networks, such as Sonic hedgehog (Shh), Bone Morphogenetic Protein (Bmp), Fibroblast Growth Factor (Fgf), and Wnt/ß-catenin signalling, is well established. These pathways are used in a reiterated fashion during development, and thus place, time, and duration of their signalling activity are all important.  In my group, we try to understand how Bmp signalling contributes to the development of orofacial structures. We use functional genomics on Bmp mouse mutants to characterise cellular and molecular processes regulated by Bmp in vivo. In this project the roles of Bmp signaling in migration and differentiation of CNC cells will be addressed. Bmp7 is expressed in CNC cells and Bmp7-deficiency affects CNC-derivatives such as Schwann cells, melanocytes, and the trigeminal ganglion. From published and preliminary data, we hypothesize that Bmp7 is critical for cytoskeletal organization, cell polarization, and dendrite formation. Bmp7-deficiency will in consequence affect cell delamination, directed migration, and cell differentiation. Using transgenic tools to visualise Bmp signalling, Bmp expression, or mark clonogenic CNC cells, in combination with micro-computer tomography (µCT), Optical Projection Tomography (OPT), and confocal microscopy, we will visualize CNC cell migration, proliferation, and differentiation in relation to and dependence of Bmp7 in 3D. Functional embryology and gene/protein expression studies will identify the stages at which Bmp7 function is critical.  Cellular assays will allow testing of direct effects of Bmp7 on CNC explant cultures. Our aim is to define molecular and cellular processes dependant on Bmp7 and establish whether the many seemingly rather different cellular outcomes are the result of fundamental changes to cytoskeletal organization. This project provides exciting opportunities for graduate and undergraduate students to receive training in cutting-edge imaging and advanced transgenic technologies, embryology, histology, and gene expression analysis including next generation sequencing, as well as benefit from national and international collaborations.
探讨骨形态发生蛋白在脑神经脊细胞中的作用 口面部是最复杂的区域。它有各种各样的形状,是几个高度专业化的结构的所在地。其发育的中心是颅神经脊细胞(Cnc)。在胚胎发育过程中,数控细胞从神经板边缘迁移到颧弓,从那里形成面部隆起和不同的组织。Cnc细胞是一种多能干细胞,可分化为骨骼、软骨、神经、牙齿、神经胶质细胞、黑素细胞和面部结缔组织。尽管只有少数细胞外信号网络,如Sonic hedgehog(Shh)、骨形态发生蛋白(BMP)、成纤维细胞生长因子(成纤维细胞生长因子)和Wnt/?-catenin信号通路的重要性已经确定,但控制其迁移、分化和增殖的信号仍然只有部分被了解。这些途径在发育过程中被反复使用,因此它们的信号活动的地点、时间和持续时间都很重要。 在我的小组中,我们试图了解BMP信号传递如何有助于口腔面部结构的发育。我们在BMP小鼠突变体上使用功能基因组学来描述体内受BMP调控的细胞和分子过程。在这个项目中,将讨论BMP信号在数控细胞迁移和分化中的作用。Bmp7在CnC细胞中表达,Bmp7缺乏影响Cnc衍生细胞,如雪旺细胞、黑素细胞和三叉神经节。根据已发表的和初步的数据,我们假设Bmp7在细胞骨架组织、细胞极化和树突形成中起关键作用。Bmp7基因缺失会影响细胞分层、定向迁移和细胞分化。使用转基因工具来可视化BMP信号、BMP表达或标记克隆性NC细胞,结合微型计算机断层扫描(µCT)、光学投影断层扫描(OPT)和共聚焦显微镜,我们将以3D可视化与Bmp7相关和依赖的CNC细胞的迁移、增殖和分化。功能胚胎学和基因/蛋白质表达研究将确定Bmp7功能的关键阶段。细胞分析将允许测试Bmp7对CNC外植体培养的直接影响。我们的目标是定义依赖于Bmp7的分子和细胞过程,并确定许多看似截然不同的细胞结果是否是细胞骨架组织发生根本性变化的结果。 该项目为研究生和本科生提供了令人兴奋的机会,让他们接受尖端成像和先进转基因技术、胚胎学、组织学和基因表达分析(包括下一代测序)方面的培训,并从国内和国际合作中受益。

项目成果

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Graf, Daniel其他文献

Addressing uncertainties in correlative imaging of exogenous particles with the tissue microanatomy with synchronous imaging strategies.
  • DOI:
    10.1093/mtomcs/mfad030
  • 发表时间:
    2023-06-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Morrell, Alexander P.;Martin, Richard A.;Roberts, Helen M.;Castillo-Michel, Hiram;Mosselmans, J. Frederick W.;Geraki, Kalotina;Warfield, Adrian T.;Lingor, Paul;Qayyum, Wasif;Graf, Daniel;Febbraio, Maria;Addison, Owen
  • 通讯作者:
    Addison, Owen
Low Serum Pyridoxine Levels Worsen Seizure Control in Adult Epilepsy Patients.
  • DOI:
    10.7759/cureus.25669
  • 发表时间:
    2022-06
  • 期刊:
  • 影响因子:
    1.2
  • 作者:
    Rane, Schweta;Elrahi, Sama;Villarreal, Joseph;Zulfi, Haneef;Fang, Xiang;Graf, Daniel;Rodriguez, Rafael;Garza, Amanda;Thottempudi, Neeharika;Rai, Prashant;Masel, Todd
  • 通讯作者:
    Masel, Todd
Sensation Seeking's Differential Role in Face-to-Face and Cyberbullying: Taking Perceived Contextual Properties Into Account
  • DOI:
    10.3389/fpsyg.2019.01572
  • 发表时间:
    2019-07-16
  • 期刊:
  • 影响因子:
    3.8
  • 作者:
    Graf, Daniel;Yanagida, Takuya;Spiel, Christiane
  • 通讯作者:
    Spiel, Christiane
Histological and molecular characterization of the growing nasal septum in mice
  • DOI:
    10.1111/joa.13332
  • 发表时间:
    2020-10-12
  • 期刊:
  • 影响因子:
    2.4
  • 作者:
    Baddam, Pranidhi;Kung, Tiffany;Graf, Daniel
  • 通讯作者:
    Graf, Daniel
Efficient calculation of beyond RPA correlation energies in the dielectric matrix formalism
  • DOI:
    10.1063/1.5025938
  • 发表时间:
    2018-05-28
  • 期刊:
  • 影响因子:
    4.4
  • 作者:
    Beuerle, Matthias;Graf, Daniel;Ochsenfeld, Christian
  • 通讯作者:
    Ochsenfeld, Christian

Graf, Daniel的其他文献

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{{ truncateString('Graf, Daniel', 18)}}的其他基金

Making a head: connecting reciprocal signaling to cell reprogramming
取得领先:将相互信号传导与细胞重编程联系起来
  • 批准号:
    RGPIN-2022-03272
  • 财政年份:
    2022
  • 资助金额:
    $ 2.48万
  • 项目类别:
    Discovery Grants Program - Individual
Probing Bone Morphogenetic Protein function in Cranial Neural Crest cells.
探索颅神经嵴细胞中的骨形态发生蛋白功能。
  • 批准号:
    RGPIN-2015-06006
  • 财政年份:
    2019
  • 资助金额:
    $ 2.48万
  • 项目类别:
    Discovery Grants Program - Individual
Probing Bone Morphogenetic Protein function in Cranial Neural Crest cells.
探索颅神经嵴细胞中的骨形态发生蛋白功能。
  • 批准号:
    RGPIN-2015-06006
  • 财政年份:
    2018
  • 资助金额:
    $ 2.48万
  • 项目类别:
    Discovery Grants Program - Individual
Probing Bone Morphogenetic Protein function in Cranial Neural Crest cells.
探索颅神经嵴细胞中的骨形态发生蛋白功能。
  • 批准号:
    RGPIN-2015-06006
  • 财政年份:
    2017
  • 资助金额:
    $ 2.48万
  • 项目类别:
    Discovery Grants Program - Individual
Probing Bone Morphogenetic Protein function in Cranial Neural Crest cells.
探索颅神经嵴细胞中的骨形态发生蛋白功能。
  • 批准号:
    RGPIN-2015-06006
  • 财政年份:
    2015
  • 资助金额:
    $ 2.48万
  • 项目类别:
    Discovery Grants Program - Individual

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骨形态发生蛋白(Bone Morphogenetic Proteins,BMP)信号在脊髓损伤中枢神经性疼痛中的作用
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  • 批准年份:
    2010
  • 资助金额:
    32.0 万元
  • 项目类别:
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