Determining the lineage progression of embryonic and adult neural stem cells

 描述(申请人提供)：神经干细胞在大脑中产生不同类型的神经元和神经胶质细胞。在大脑皮层，皮质投射神经元按顺序排列 是由放射状胶质细胞产生的。深层神经元首先诞生，其次是上层神经元。然而，调节放射状胶质细胞产生这些不同类型细胞的细胞机制还不是很清楚，也是有争议的。已经提出了两种不同的模型。早期细胞移植实验、病毒谱系追踪和体外细胞谱系分析提出了一种模型，该模型假设早期放射状胶质细胞(RGC)具有多能性，并根据出生日期依次产生不同类型的神经细胞和胶质细胞。已经提出了一个新的模型，该模型假设早期的视网膜节细胞含有固有的谱系受限的干细胞，这些干细胞继而产生特定的神经元亚型。我们建议测试这些不同的模型，并确定在皮质发育过程中产生不同投射神经元亚型和胶质细胞的细胞机制。我们还将确定在健康的成年哺乳动物脑中是否存在多潜能的成人神经干细胞。

 DESCRIPTION (provided by applicant): Neural stem cells generate the diverse neuronal and glial cell types in the brain. In the cerebral cortex, cortical projection neurons are sequentially generated from the radial glial cells. The deep-layer neurons are born first, followed by upper-layer neurons. However, the cellular mechanism that regulates the radial glial cells to generate these diverse cell types is not well understood and is controversial. Two different models have been proposed. Early cell transplantation experiments, viral lineage tracing and in vitro cell lineage analysis suggested a model that postulates that early radial glial cells (RGCs) are multipotent, and sequentially generate different neural cell types and glia based on birthdate. A new model has been proposed that postulates that the early RGCs contain intrinsically lineage restricted stem cells which in turn give rise to specific neuronal subtypes. We propose to test these different models and determine the cellular mechanisms underlying the generation of different projection neuron subtypes and glia during cortical development. We will also determine whether multipotent adult neural stem cells exist in healthy adult mammalian brains.