Determining the lineage progression of embryonic and adult neural stem cells

 描述（由申请人提供）：神经干细胞在大脑中产生多种神经元和神经胶质细胞类型。在大脑皮层，皮层投射神经元依次 由放射状神经胶质细胞产生。深层神经元首先诞生，然后是上层神经元。然而，调节放射状神经胶质细胞产生这些不同细胞类型的细胞机制还没有很好地理解，是有争议的。提出了两种不同的模式。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，该模型假定早期放射状胶质细胞（RGC）是多能的，并且基于出生日期依次产生不同的神经细胞类型和胶质细胞。已经提出了一种新的模型，该模型假设早期RGC含有内在谱系限制的干细胞，这些干细胞进而产生特定的神经元亚型。我们建议测试这些不同的模型，并确定不同的投射神经元亚型和神经胶质细胞在皮层发育过程中产生的细胞机制。我们还将确定多能成体神经干细胞是否存在于健康的成年哺乳动物大脑中。

 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.