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

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

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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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腺嘌呤核苷酸转位酶在慢性阻塞性肺病(COPD)线粒体功能相关衰老中的作用
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    10794933
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    2022
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使用 FRET 开发 miRNA 和腺嘌呤甲基转移酶的诺贝尔检测方法
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健康老龄化和阿尔茨海默病脑细胞 DNA 腺嘌呤甲基化的批判性评估
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DNA Methylation at N6-Adenine in Placental Trophoblast Development
胎盘滋养层发育中 N6-腺嘌呤 DNA 甲基化
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