Mechanisms patterning the midface
中面部图案化机制
基本信息
- 批准号:10812765
- 负责人:
- 金额:$ 42.86万
- 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:2023-09-18 至 2028-06-30
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAffectAntibodiesBindingBinding SitesBone structureCell Differentiation processCellsChIP-seqCodeColorCongenital AbnormalityDataDevelopmentDisease modelDysmorphologyElementsEmbryonic DevelopmentEnhancersEtiologyEyeFaceFrontonasal dysplasiaGene CombinationsGene ExpressionGenesGeneticGenetic DiseasesGenetic TranscriptionGenomeGenomicsHeadHealthHi-CHumanHuman GeneticsIn Situ HybridizationJawMapsMediatingMethodsMissionModelingMolecularMutationNational Institute of Dental and Craniofacial ResearchNeural Crest CellNoseOrthologous GenePatternPhenotypePositioning AttributeProteinsPublishingReporterResearchResolutionShapesSkeletonSpecific qualifier valueStructureSystemTestingTimeTransgenesWorkZebrafishcartilaginouschromatin immunoprecipitationcraniofacialcraniofacial developmentdomain mappingexperimental studygene functionhuman diseaseimprovedin vivoinnovationmutantparalogous geneprogenitorpromotersingle-cell RNA sequencingskeletalsuccesstranscription factorvertebrate genomezebrafish development
项目摘要
PROJECT SUMMARY/ABSTRACT: The long-term objective of this proposal is to understand formation of the
midface skeleton, both during normal development, and in human genetic disease conditions. The midface
consists of the structures around the nose, the eye, and the upper jaw. Human genetic disorders, like
frontonasal dysplasia, affect these midface structures. Specifically, the ALX transcription factor encoding genes
have been implicated in multiple types of frontonasal dysplasia. Uniquely, we model these diseases in
zebrafish by using genetic mutants. We propose that the ALX genes function to specify an identity code which
patterns the vertebrate midface. Our model draws from examples like the DLX and HOX codes, which specify
identity in the dorsoventral and anteroposterior axes of the craniofacial skeleton, respectively. We propose
three specific aims to test our innovative “alx-bullseye code” hypothesis, that nested alx gene expression
directly regulates frontonasal skeletal identity. In Aim 1 we define the skeletal structures arising from the
alx-bullseye code in wild types using in situ hybridization, live cell tracking, and lineage tracing. Aim 2 will
determine whether alx gene combinations function to specify frontonasal identity. To identify these functions,
we will compare wild types to alx mutants examining gene expression, skeletal cell differentiation, and
misexpression phenotypes. Aim 3 will uncover how alx genes molecularly control cellular identity. We will
examine an in vivo Alx direct transcriptional reporter, ChIP-seq to identify Alx protein occupancy across the
genome, and Hi-C to reveal enhancer-promoter contacts mediated by Alx. Significance of this proposal is high,
the genes that we propose function in the alx bullseye code have direct human orthologs that are associated
with midface dysmorphologies. This proposal is innovative, as there has not yet been a patterning code
proposed for the vertebrate midface. Success of this proposal will enhance our understanding of midface
craniofacial development and human disease. By using the strengths of the zebrafish system to elucidate the
molecular, cellular, and genetic mechanisms underlying frontonasal dysplasia, we are fulfilling the mission of
the NIDCR to improve human health through research.
项目摘要/摘要:本提案的长期目标是了解形成的
项目成果
期刊论文数量(0)
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James Tucker Nichols其他文献
James Tucker Nichols的其他文献
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{{ truncateString('James Tucker Nichols', 18)}}的其他基金
The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis
颌关节形态发生的分子遗传学和细胞生物学
- 批准号:
8016707 - 财政年份:2009
- 资助金额:
$ 42.86万 - 项目类别:
The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis
颌关节形态发生的分子遗传学和细胞生物学
- 批准号:
7790556 - 财政年份:2009
- 资助金额:
$ 42.86万 - 项目类别:
The Molecular Genetics and Cell Biology of Jaw Joint Morphogenesis
颌关节形态发生的分子遗传学和细胞生物学
- 批准号:
7546014 - 财政年份:2009
- 资助金额:
$ 42.86万 - 项目类别:
Imaging Delta-Induced Activation of Notch
成像 Delta 诱导的 Notch 激活
- 批准号:
7386757 - 财政年份:2007
- 资助金额:
$ 42.86万 - 项目类别:
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