The Role of FAM20B-Catalyzed Proteoglycans in Tooth Development
FAM20B 催化蛋白多糖在牙齿发育中的作用
基本信息
- 批准号:10471850
- 负责人:
- 金额:$ 14.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-18 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAddressAreaBiological ProcessCell surfaceCellsDataDentalDentitionDevelopmentDiseaseDoseEmbryoEnamel OrganEpithelialEquilibriumEtiologyExtracellular MatrixFamilyFundingGenesGlycosaminoglycansGrantGrowth FactorHumanIn VitroIncisorKnowledgeLightLocationMediatingMolecularMusOrgan Culture TechniquesPathologic ProcessesPatternPhenotypePhosphotransferasesPilot ProjectsPlayProteinsProteoglycanRegulationResearchResearch PersonnelRodentRoleScienceScientistSecureSideSignal TransductionSignaling MoleculeSiteSupernumerary ToothTestingTherapeuticTimeTissuesTooth regenerationTooth structureUnited States National Institutes of HealthWNT Signaling PathwayWagesXyloseadenoviral-mediatedcareerdesignepithelial stem cellexperimental studyextracellularinhibitorinsightknock-downmembermorphogensmutantnoveloverexpressionprogramsstem cell divisionstem cellstranscription factor
项目摘要
Project summary/Abstract
The candidate received his first R01 grant in April 2017. At this critical point of his career, he needs at least
75% of protected time on research to develop into the type of scientist he wants to become and secure NIH
funding as an independent scientist after this R01 grant is completed. The R01 project is summarized below.
Supernumerary teeth can cause a broad range of dental complications. As extra teeth are formed on
existing dentition, unraveling the molecular mechanism of supernumerary tooth formation will not only help
develop the therapeutic strategy for this disease but also provide insights into tooth regeneration. Despite
the significant progress in understanding the regulatory role of morphogens, growth factors, and
transcriptional factors in supernumerary tooth formation, little is known about the role of extracellular
components such as proteoglycans in this pathological process. The candidate’s recent studies show that
inactivation of dental epithelial Fam20B, a newly discovered xylose kinase essential for glycosaminoglycan
(GAG) assembly, leads to supernumerary incisors in mice. Their pilot study reveals that GAG deficiency in
the dental epithelium leads to ectopic activation of WNT signaling, and that an ectopic Sox2 expression is
located in the same area, which normally should disappear from this site after E14.5. Their in vitro study
shows that GAGs on certain FAM20B-catalyzed proteoglycans suppress WNT signaling but facilitate Wise-
mediated inhibition on WNT. Conversely, administering WNT inhibitor to the mutant embryos rescued the
tooth phenotype in some cases. These data led the candidate to form his central hypothesis that certain
FAM20B-catalyzed proteoglycans regulate tooth renewal by mediating the stem cell renewal via negative
regulation on WNT signaling in the dental epithelium. He proposes three specific aims to test this
hypothesis: (1) To determine if FAM20B-catalyzed proteoglycans mediate tooth renewal via negative
regulation on WNT signaling, and if GAG-mediated Wise inhibition on WNT underlies the supernumerary
tooth formation. (2) To determine whether FAM20B-catalyzed proteoglycans regulate tooth renewal by
mediating stem cell renewal in the dental epithelium, and (3) To identify the proteoglycans responsible for
the supernumerary tooth formation. The completion of this study will advance the understanding about the
molecular mechanism underlying supernumerary tooth formation and help in laying the groundwork for tooth
regeneration. As FAM20B and proteoglycans are extensively present in many tissues, the knowledge
gained from this study may shed light on the proteoglycan-mediated signaling in other tissues.
项目摘要/摘要
候选人于2017年4月获得了他的第一笔R01赠款。在他职业生涯的关键时刻,他至少需要
75%的受保护时间的研究时间发展成为他想要成为并确保NIH的科学家的类型
这笔R01赠款完成后,作为独立科学家的资助。 R01项目在下面总结。
上牙可能会引起广泛的牙齿并发症。随着额外的牙齿形成
现有的牙列,阐明了超生物牙齿形成的分子机制不仅有助于
制定该疾病的治疗策略,但也为牙齿再生提供了见解。尽管
理解形态因素,生长因素和
在超级牙齿形成中的转录因子,对细胞外的作用知之甚少
在此病理过程中,诸如蛋白聚糖之类的成分。候选人最近的研究表明
牙齿上皮FAM20B的失活,这是一种新发现的木糖激酶,对于糖胺聚糖必不可少
(堵嘴)组装,导致小鼠的超努门牙。他们的试点研究表明,
牙齿上皮导致Wnt信号的生态激活,并且异位SOX2表达是
位于同一区域,通常应在E14.5之后从该站点消失。他们的体外研究
表明在某些FAM20B催化的蛋白聚糖上的插科打d抑制了Wnt信号,但有助于明智
介导的抑制Wnt。相反,将Wnt抑制剂施用到突变胚胎中恢复了
在某些情况下,牙齿表型。这些数据导致候选人形成了他的中心假设
FAM20B催化的蛋白聚糖通过通过阴性介导干细胞更新来调节牙齿更新
对牙齿上皮中Wnt信号传导的调节。他提出三个特定目标来测试这一点
假设:(1)确定FAM20B催化的蛋白聚糖是否通过阴性介导牙齿更新
对Wnt信号的调节,如果GAG介导的WISE对Wnt的明智抑制是超生物的基础
形成牙齿。 (2)确定FAM20B催化的蛋白聚糖是否通过
介导牙齿上皮中的干细胞更新,(3)确定负责的蛋白聚糖
超牙的形成。这项研究的完成将促进对
超级牙齿形成的分子机制,有助于牙齿奠定基础
再生。由于FAM20B和蛋白聚糖在许多组织中广泛存在,因此知识
从这项研究中获得的可能会阐明其他组织中蛋白聚糖介导的信号传导。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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XIAOFANG WANG其他文献
XIAOFANG WANG的其他文献
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{{ truncateString('XIAOFANG WANG', 18)}}的其他基金
The Role of FAM20B-catalyzed Proteoglycans in Tooth Development
FAM20B 催化蛋白多糖在牙齿发育中的作用
- 批准号:
9899242 - 财政年份:2017
- 资助金额:
$ 14.92万 - 项目类别:
Role of FAM20C in the Phosphorylation of SIBLING Protein
FAM20C 在 SIBLING 蛋白磷酸化中的作用
- 批准号:
8817274 - 财政年份:2014
- 资助金额:
$ 14.92万 - 项目类别:
Role of FAM20C in the Phosphorylation of SIBLING Protein
FAM20C 在 SIBLING 蛋白磷酸化中的作用
- 批准号:
8622956 - 财政年份:2014
- 资助金额:
$ 14.92万 - 项目类别:
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