Diversification of cell types in the Drosophila retina - Resubmission - 1
果蝇视网膜细胞类型的多样化 - 重新提交 - 1
基本信息
- 批准号:10328555
- 负责人:
- 金额:$ 24.66万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Activities of Daily LivingAdenineBinding SitesCell Differentiation processCellsComplexConeDNAData SetDevelopmentDevelopmental BiologyDifferentiated GeneDrosophila eyeDrosophila genusEGFR geneElementsEnhancersEpidermal Growth Factor ReceptorEyeEye DevelopmentEye diseasesFeedsGene ExpressionGenesGeneticGenetic DiseasesGenetic TranscriptionGenomicsGlassGoalsIndividualInjuryLightMediatingMethodsMethyltransferaseMitoticMolecularNeural RetinaNeurogliaNeuronsNucleic Acid Regulatory SequencesOrganOutputPathway interactionsPatternPhotoreceptorsPigmentsProcessReceptor Protein-Tyrosine KinasesReceptor SignalingRegenerative MedicineRegulationRetinaRetinal ConeSignal PathwaySignal TransductionSpecific qualifier valueSpecificitySystemTestingTo specifyTranscription RepressorUndifferentiatedVisionWorkZinc Fingerscell fate specificationcell replacement therapycell typedesignexperimental studyextracellularflygenetic analysisimprovedlensmutantpreventprogenitorprogramsretinal regenerationscreeningstem cellstranscription factortranscriptomics
项目摘要
Summary
The development of a complex organ such as the eye involves the specification of multiple distinct
cell types and the integration of their functions. In Drosophila, the light-detecting photoreceptors and the
glial-like cone and pigment cells that secrete the lens and produce screening pigments arise from a single
field of equivalent progenitors. Commitment to one of these cell fates requires extracellular signals to be
integrated with a complex network of intrinsic transcription factors. Although receptor tyrosine kinase
signaling has been known for many years to induce both photoreceptors and cone cells, most of its target
genes remain unknown. It is also unclear which intrinsic transcription factors distinguish these cell identities.
The zinc finger transcription factor Glass had been thought to specify the photoreceptor fate, but our recent
work showed that it acts in each of the three cell types to promote their normal differentiation. This proposal
seeks to understand how these common factors activate distinct differentiation pathways. The first aim will
look for direct target genes of receptor tyrosine kinase signaling and Glass during retinal differentiation.
Targeted DNA adenine methyltransferase identification (DamID) will be used to identify direct target genes
of Pointed, the transcription factor that mediates Epidermal growth factor receptor (EGFR) signaling, in
undifferentiated cells, photoreceptors and cone cells. A similar approach will be used to identify Glass target
genes, and both datasets will be compared to transcriptomic analysis of genes that change their expression
in Egfr or glass mutants. The goal of these experiments is to identify transcription factors that are induced
by EGFR signaling to promote the differentiation of photoreceptors and cone cells, and elucidate how Glass
feeds into their regulation. The second aim concerns how transcriptional repressors restrict the effects of
Glass to drive cell type-specific gene expression. Two defined regulatory regions that are known to drive
photoreceptor-specific expression in a Glass-dependent manner will be used to identify repressors that
prevent Glass from activating these genes in cone and pigment cells. The importance of these repressor
binding sites will be tested in the endogenous genomic context. In a complementary approach, enhancer
regions that drive Glass-dependent expression specifically in cone or pigment cells will be identified and
their regulation characterized. In combination, these experiments will reveal how distinct cell identities can
be specified from common progenitors using a limited set of signals and transcription factors, a process that
also occurs in the mammalian retina. The results will help to refine our ability to produce specific cell types
from stem cells for regenerative medicine.
总结
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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Jessica E Treisman其他文献
Jessica E Treisman的其他文献
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{{ truncateString('Jessica E Treisman', 18)}}的其他基金
Mechanisms of development of curved refractive surfaces
弯曲折射表面的发展机制
- 批准号:
10624979 - 财政年份:2022
- 资助金额:
$ 24.66万 - 项目类别:
Mechanisms of development of curved refractive surfaces
弯曲折射表面的发展机制
- 批准号:
10443019 - 财政年份:2022
- 资助金额:
$ 24.66万 - 项目类别:
Specialized junctions in the development of epithelia and neural circuits
上皮细胞和神经回路发育中的特殊连接
- 批准号:
10221016 - 财政年份:2020
- 资助金额:
$ 24.66万 - 项目类别:
Specialized junctions in the development of epithelia and neural circuits
上皮细胞和神经回路发育中的特殊连接
- 批准号:
10040885 - 财政年份:2020
- 资助金额:
$ 24.66万 - 项目类别:
Interactive Processes in Photoreceptor Axon Targeting
光感受器轴突靶向中的交互过程
- 批准号:
10633287 - 财政年份:2019
- 资助金额:
$ 24.66万 - 项目类别:
Interactive processes in photoreceptor axon targeting
光感受器轴突靶向中的交互过程
- 批准号:
10183353 - 财政年份:2019
- 资助金额:
$ 24.66万 - 项目类别:
Interactive processes in photoreceptor axon targeting
光感受器轴突靶向中的交互过程
- 批准号:
10412062 - 财政年份:2019
- 资助金额:
$ 24.66万 - 项目类别:
Interactive processes in photoreceptor axon targeting
光感受器轴突靶向中的交互过程
- 批准号:
10631741 - 财政年份:2019
- 资助金额:
$ 24.66万 - 项目类别:
Interactive processes in photoreceptor axon targeting
光感受器轴突靶向中的交互过程
- 批准号:
9796954 - 财政年份:2019
- 资助金额:
$ 24.66万 - 项目类别:
Interactive processes in photoreceptor axon targeting
光感受器轴突靶向中的交互过程
- 批准号:
10162404 - 财政年份:2019
- 资助金额:
$ 24.66万 - 项目类别:
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