Developmental Timing During Cortical Development

皮质发育期间的发育时间

基本信息

项目摘要

Summary/Abstract The human cerebral cortex contains an astonishing diversity of cell types distributed across dozens of functional areas, which emerge during early development for an apparently uniform neuroepithelium. It has long been hypothesized that genetic mutations underlying brain development abnormalities and genes implicated in neurodevelopmental psychiatric disorders can impact brain development in a variety of ways, but we currently lack scalable tools for interrogating their impact on the development of specialized cell types. Astrocytes represent a highly diverse cell class that is broadly categorized into a handful of cardinal types. Astrocytes emerge in late development, and selective vulnerabilities of astrocyte subtypes to mutations or environmental perturbations may underlie distinct phenotypes in psychiatric disorders or in Zika virus infection. However, developmental origins, molecular characteristics, and mechanisms of subtype specification are poorly understood. We currently lack experimental methods to study human astrocyte subtypes and their development. Our preliminary data suggest that at mid-gestation, radial glia subtypes may be biased towards generating different subtypes of human astrocytes. In the proposed project we propose to extend this finding by mapping the temporal dynamics of cellular differentiation from radial glia subtypes across multiple stages of development. We will also determine whether similar developmental dynamics take place in ferret, which could serve as a substitute to human tissue and enable in vivo functional studies. Secondly, we will determine developmental lineage relationships between cortical radial glia subtypes and astrocyte subtypes. Our preliminary studies predict morphologically distinct subtypes of astrocytes emerge from anatomically distinct germinal niches, and we propose to directly register these morphotypes to transcriptomic identities using single cell mRNA sequencing. Finally, our goal is to understand whether distinct radial glia subtypes contribute distinct cell types of the cerebral cortex. To address this question, we propose to perform xenotransplantation experiments into mouse brain. We will combine this approach with single cell sequencing, and in silico analyses co-embedding our data with existing resources from adult human cortex to reveal what molecular subtypes may emerge from transcriptomically- distinct subtypes of cortical progenitor cells.
摘要/文摘

项目成果

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Tomasz Nowakowski其他文献

Tomasz Nowakowski的其他文献

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{{ truncateString('Tomasz Nowakowski', 18)}}的其他基金

Neurodevelopmental defects of the thalamocortical pathway as a convergent feature of psychiatric disorders
丘脑皮质通路的神经发育缺陷是精神疾病的共同特征
  • 批准号:
    10655225
  • 财政年份:
    2023
  • 资助金额:
    $ 39.46万
  • 项目类别:
Directed Evolution of Novel AAVs and Regulatory Elements for Selective Microglial Gene Expression
新型 AAV 和选择性小胶质细胞基因表达调控元件的定向进化
  • 批准号:
    10587795
  • 财政年份:
    2023
  • 资助金额:
    $ 39.46万
  • 项目类别:
Developmental Timing During Cortical Development
皮质发育期间的发育时间
  • 批准号:
    10446603
  • 财政年份:
    2022
  • 资助金额:
    $ 39.46万
  • 项目类别:
Machine Learning Augmented Discovery of AAV Capsids for Cell Type Specific Access into Human Neurons and Glia
机器学习增强了 AAV 衣壳的发现,用于特定细胞类型进入人类神经元和神经胶质细胞
  • 批准号:
    10512547
  • 财政年份:
    2022
  • 资助金额:
    $ 39.46万
  • 项目类别:

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