Admin Supplement: Role of Shh/Brachyury axis in the maintenance of the postnatal intervertebral disc
管理补充:Shh/Brachyury 轴在产后椎间盘维护中的作用
基本信息
- 批准号:10879520
- 负责人:
- 金额:$ 26.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-15 至 2026-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAffectAgeAgingAtlasesBrachyury proteinCatalogsCellsChronic low back painCodeCollectionData SetDatabasesDefectDevelopmentDifferentiation and GrowthEcosystemEmbryoEmbryonic StructuresFundingFutureGenesGeneticGenotype-Tissue Expression ProjectGoalsGrowthHealthHereditary DiseaseHeterozygoteHistologicHumanInjuryInternationalIntervertebral disc structureKnock-outKnockout MiceKnowledgeLearningLigandsMaintenanceMolecularMorphologyMusNatural regenerationOnline Mendelian Inheritance In ManPainPathologicPathologyPersonsPhenotypePopulationProcessProteinsPublishingQuality of lifeRejuvenationReportingResearchResourcesRoleSHH geneSignal TransductionSkeletonStandardizationStructureTestingTherapeuticUnited States National Institutes of HealthVertebral columnWorkage relatedchronic back paindata portaleffective therapyexperimental studygastrulationgene functiongenome wide association studygenome-wideinsightintervertebral disk degenerationknockout genemouse genomemouse modelmutantneonatal micenotochordnovelnucleus pulposusparent grantpathological agingpostnatalpostnatal developmentprogramsprotein protein interactionscreeningsexskeletalsmoothened signaling pathwaytargeted treatmenttranscription factortranscriptome sequencing
项目摘要
PROJECT SUMMARY/ ABSTRACT
Mechanisms that regulate the formation and development of the intervertebral discs (IVDs) of the spine are not
well understood. Our current limited knowledge of the formation of the IVDs is built on genetic mouse models,
but much remains to be learned. Degenerative disc disease (DDD) is a leading cause of chronic low back pain
(cLBP), affecting the mobility and quality of life of millions of people worldwide, however, with no therapeutics or
cure. A better understanding of the cellular and molecular basis of the formation, development, and maintenance
of healthy IVD will help test the role of key developmental molecules in the regeneration of rejuvenation of the
IVDs. NIH Common Fund datasets generated by the Knockout Mouse Phenotyping Program (KOMP), a part of
the International Mouse Phenotyping Consortium (IMPC), is a genome-wide collection of mouse knockouts. The
goal of KOMP and IMPC is to generate a catalog of mammalian gene function, by knocking out every protein-
coding gene in the mouse genome, and deeply phenotype to understand its role in human health. A standardized
phenotyping pipeline is followed by the 21 research centers where the single-gene knockout mice are being
generated and phenotyped in both sexes. Our overarching hypothesis underlying this work is that a better
understanding of the genes and their network that regulate intervertebral disc (IVD, or disc) development and
maintenance, and can provide molecular insights into IVD pathologies. Previously we reported that BRA, a
critical developmental regulator is also expressed by postnatal nucleus pulposus (NP) cells of the IVDs and that
the expression of BRA declines with pathological IVD aging. NP cells are descendants of the embryonic
notochord, and our previous work showed the postnatal NP continues to act as the signaling center and regulate
the growth and differentiation of surrounding cells via SHH signaling. The goal of the proposed study is
to substantially leverage NIH Common Fund KOMP and GTEx portal datasets along with non-CF datasets like
STRING-db, OMIM, and publicly available GWAS datasets to screen novel genes required for IVD development
and maintenance. We will systematically prioritize genes to characterize the effect of their loss on IVD
development and maintenance using the single-KO knockouts generated and characterized by IMPC, that are
viable in heterozygous or homozygous conditions, have axial skeleton defects and are relevant to human health
using our screening pipeline. Completion of the proposed study will identify novel genes relevant to IVD, and
future mechanistic studies can test the hypothesis related to their specific roles in IVD formation, differentiation,
or health maintenance.
项目摘要/摘要
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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Chitra L Dahia其他文献
Chitra L Dahia的其他文献
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{{ truncateString('Chitra L Dahia', 18)}}的其他基金
Role of Developmental Signaling Pathways in Maintenance of Spinal Discs
发育信号通路在椎间盘维护中的作用
- 批准号:
10305941 - 财政年份:2021
- 资助金额:
$ 26.85万 - 项目类别:
Role of Developmental Signaling Pathways in Maintenance of Spinal Discs
发育信号通路在椎间盘维护中的作用
- 批准号:
10609916 - 财政年份:2021
- 资助金额:
$ 26.85万 - 项目类别:
Role of Shh/Brachyury axis in the maintenance of the postnatal intervertebral disc
Shh/Brachyury 轴在产后椎间盘维持中的作用
- 批准号:
10596619 - 财政年份:2021
- 资助金额:
$ 26.85万 - 项目类别:
Role of Developmental Signaling Pathways in Maintenance of Spinal Discs
发育信号通路在椎间盘维护中的作用
- 批准号:
10469481 - 财政年份:2021
- 资助金额:
$ 26.85万 - 项目类别:
Role of Shh/Brachyury axis in the maintenance of the postnatal intervertebral disc
Shh/Brachyury 轴在产后椎间盘维持中的作用
- 批准号:
10433845 - 财政年份:2021
- 资助金额:
$ 26.85万 - 项目类别:
A Wnt/Shh signaling loop controls intervertebral disc growth and differentiation
Wnt/Shh 信号环路控制椎间盘生长和分化
- 批准号:
8759103 - 财政年份:2014
- 资助金额:
$ 26.85万 - 项目类别:
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