NOVEL SCREEN FOR MINERALIZED CRANIOFACIAL AND TOOTH MUTANTS IN ZEBRAFISH
斑马鱼矿化颅面和牙齿突变体的新型筛查
基本信息
- 批准号:7577329
- 负责人:
- 金额:$ 39.21万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-02-01 至 2011-01-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelAwardBindingBiological AssayBiological Response Modifier TherapyCatalogingCatalogsChemicalsCleft LipComplexComplicationCraniosynostosisDNADataDefectDevelopmentEthylnitrosoureaExhibitsFamilyGene MutationGenesGeneticGenomicsGoalsGrantGrowth and Development functionHumanHuman DevelopmentIn VitroJoint structure of suture of skullKnowledgeLaboratoriesLeftLifeMammalsMapsMethodsModelingMolecularMolecular GeneticsMolecular TargetMusMutagenesisNational Institute of Dental and Craniofacial ResearchNatural regenerationNatureOperative Surgical ProceduresPalatePathologyPathway interactionsPenetranceProteinsResearchResearch DesignResearch PersonnelSample SizeSignal TransductionSkeletal DevelopmentSupernumerary ToothTestingTimeTissue SampleTissuesTooth LossTooth structureWorkZebrafishbasecartilage developmentclinically relevantcraniofacialcraniofacial repairdesignexperiencegene conservationgene functiongene therapygenetic analysishuman tissuein vivoinnovationmutantnovelprematureprogramsreceptorrepairedskeletalskeletogenesissuture fusion
项目摘要
DESCRIPTION (provided by applicant): The broad objective of this study is to identify molecular targets regulating zebrafish craniofacial skeletogenesis and primary and replacement tooth formation (RTF), that can be manipulated to repair human craniofacial skeletal and tooth defects in humans. Although significant research efforts have resulted in the identificaton of certain gene mutations responsible for human craniofacial skeletal defects, functional characterizations have been hampered by limited availability of human tissues and suitable animal models. Similarly, clinically relevant biological therapies to regenerate teeth do not currently exist, and research on tooth regeneration strategies is hampered by similar limitations. Targeted, molecular based therapies to effectively and permanently correct mineralized craniofacial and tooth defects would be a significant advancement over current surgical repair methods. The fact that zebrafish craniofacial skeletal development closely resembles that of mammals, combined with the fact that zebrafish continuously regenerate teeth throughout their lives, provides a unique opportunity to define and funcitionally characterize molecular signaling cascades directing mineralized craniofacial skeletal and replacement tooth development. The extensive conservation of gene identity, genomic organization and gene function between zebrafish and humans allows for studies in zebrafish to be directly related to human development. Our long term goal is to identify genetic pathways that can be manipulated to repair craniofacial skeletal defects and initiate RTF in humans. The objective of this study is to exploit the zebrafish to perform functional studies of molecular mechanisms regulating craniofacial mineralized skeletal and tooth formation. In this proposal we will first perform a forward genetic ENU mutagenesis screen, combined with a sensitive in vivo assay for mineralized tissue formation, to identify novel craniofacial skeletal and RTF mutants. Next, we will confirm the molecular identity, and perform functional characterization, of each identified mutant. We anticipate that the proposed studies will reveal molecular signaling cascades that may facilitate the implementation of clinically relevant gene based therapies to correct mineralized craniofacial skeletal and tooth defects in humans.
描述(由申请人提供):这项研究的广泛目标是确定调节斑马鱼颅骨骨骼发生以及一级和替代牙齿形成(RTF)的分子靶标,可以操纵人类的人类颅骨骨骼和牙齿缺陷。尽管重大的研究工作导致了某些负责人颅面骨骼缺陷的某些基因突变的识别,但人类组织的可用性有限和合适的动物模型受到了障碍,但功能特征受到阻碍。同样,目前不存在与牙齿再生的临床相关生物学疗法,并且对牙齿再生策略的研究受到类似局限性的阻碍。针对性的,基于分子的疗法可有效,永久纠正矿物质颅面和牙齿缺陷,将是当前手术修复方法的显着进步。斑马鱼颅颅骨骼发育与哺乳动物的骨骼发育非常相似,再加上斑马鱼一生不断再生牙齿,提供了一个独特的机会,可以定义和函数来定义分子信号级联,指导矿化的颅面颅骨骨骼和替代牙齿发育。斑马鱼和人类之间基因认同,基因组组织和基因功能的广泛保护允许在斑马鱼中进行研究与人类发展直接相关。我们的长期目标是确定可以操纵的遗传途径来修复颅面骨骼缺陷并在人类中启动RTF。这项研究的目的是利用斑马鱼进行调节颅面矿化骨骼和牙齿形成的分子机制的功能研究。在此提案中,我们将首先执行一个正向遗传ENU诱变筛选,并结合对矿化组织形成的敏感体内测定,以鉴定新型的颅面骨骼和RTF突变体。接下来,我们将确认每个已鉴定的突变体的分子身份并执行功能表征。我们预计拟议的研究将揭示分子信号传导级联反应,这可能有助于实施临床相关基因的疗法,以纠正人类中矿化的颅面骨骼和牙齿缺陷。
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Morphogenesis of the zebrafish jaw: development beyond the embryo.
斑马鱼颌的形态发生:胚胎以外的发育。
- DOI:10.1016/b978-0-12-387036-0.00011-6
- 发表时间:2011
- 期刊:
- 影响因子:0
- 作者:Parsons,KevinJ;Andreeva,Viktoria;JamesCooper,W;Yelick,PamelaC;CraigAlbertson,R
- 通讯作者:CraigAlbertson,R
Identification of adult mineralized tissue zebrafish mutants.
- DOI:10.1002/dvg.20712
- 发表时间:2011-04
- 期刊:
- 影响因子:1.5
- 作者:Andreeva, Viktoria;Connolly, Michelle H.;Stewart-Swift, Caitlin;Fraher, Daniel;Burt, Jeffrey;Cardarelli, Justin;Yelick, Pamela C.
- 通讯作者:Yelick, Pamela C.
Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.
- DOI:10.1371/journal.pbio.3002008
- 发表时间:2023-03
- 期刊:
- 影响因子:9.8
- 作者:Xie, Haibo;Kang, Yunsi;Liu, Junjun;Huang, Min;Dai, Zhicheng;Shi, Jiale;Wang, Shuo;Li, Lanqin;Li, Yuan;Zheng, Pengfei;Sun, Yi;Han, Qize C.;Zhang, Jingjing;Zhu, Zezhang;Xu, Leilei;Yelick, Pamela;Cao, Muqing;Zhao, Chengtian
- 通讯作者:Zhao, Chengtian
Animal models of fibrodysplasia ossificans progressiva.
- DOI:10.1002/dvdy.24606
- 发表时间:2018-03
- 期刊:
- 影响因子:0
- 作者:LaBonty M;Yelick PC
- 通讯作者:Yelick PC
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PAMELA C YELICK其他文献
PAMELA C YELICK的其他文献
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{{ truncateString('PAMELA C YELICK', 18)}}的其他基金
2022 Craniofacial Morphogenesis and Tissue Regeneration Gordon Research Conference and Gordon Research Seminar
2022颅面形态发生与组织再生戈登研究会议暨戈登研究研讨会
- 批准号:
10388749 - 财政年份:2022
- 资助金额:
$ 39.21万 - 项目类别:
2020 Cranifacial Morphogenesis and Tissue Regeneration GRC/GRS
2020 颅面形态发生与组织再生 GRC/GRS
- 批准号:
9912417 - 财政年份:2020
- 资助金额:
$ 39.21万 - 项目类别:
Bioengineered Composite Alveolar Bone-Tooth Constructs for Tooth Regeneration
用于牙齿再生的生物工程复合牙槽骨牙齿结构
- 批准号:
9975806 - 财政年份:2017
- 资助金额:
$ 39.21万 - 项目类别:
Novel Zebrafish Models for Human Fibrodysplasia Ossificans Progressiva
人类进行性骨化纤维发育不良的新型斑马鱼模型
- 批准号:
9369566 - 财政年份:2017
- 资助金额:
$ 39.21万 - 项目类别:
Bioengineered Composite Alveolar Bone-Tooth Constructs for Tooth Regeneration
用于牙齿再生的生物工程复合牙槽骨牙齿结构
- 批准号:
10192702 - 财政年份:2017
- 资助金额:
$ 39.21万 - 项目类别:
Bioengineered Composite Alveolar Bone-Tooth Constructs for Tooth Regeneration
用于牙齿再生的生物工程复合牙槽骨牙齿结构
- 批准号:
9444207 - 财政年份:2017
- 资助金额:
$ 39.21万 - 项目类别:
The zebrafish mutant droog as a model for human osteoporosis
斑马鱼突变体 droog 作为人类骨质疏松症模型
- 批准号:
8774474 - 财政年份:2014
- 资助金额:
$ 39.21万 - 项目类别:
Alk8 Regulation of Replacement Tooth Formation
Alk8 替换牙齿形成的调节
- 批准号:
7911867 - 财政年份:2009
- 资助金额:
$ 39.21万 - 项目类别:
Alk8 Regulation of Replacement Tooth Formation
Alk8 替换牙齿形成的调节
- 批准号:
7741060 - 财政年份:2009
- 资助金额:
$ 39.21万 - 项目类别:
NOVEL SCREEN FOR MINERALIZED CRANIOFACIAL AND TOOTH MUTANTS IN ZEBRAFISH
斑马鱼矿化颅面和牙齿突变体的新型筛查
- 批准号:
7191891 - 财政年份:2007
- 资助金额:
$ 39.21万 - 项目类别:
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