Apoptosis and Renewal of Neural Progenitor Cells

这项建议是一个有竞争力的更新申请，我们的研究计划的作用，胱天蛋白酶 蛋白酶家族，c-Jun NH 2-末端激酶（JNK）和磷脂酰丝氨酸受体（PSR）， 脑发育和神经系统疾病中的神经元凋亡。在本项目中，我们将 我们对这些信号通路的研究，新的重点是细胞凋亡和更新的机制， 神经前体细胞 目的1：研究磷脂酰丝氨酸和磷脂酰丝氨酸下游的作用机制 受体（PS-PSR）识别导致神经祖细胞凋亡。我们将在 外细胞表面的神经祖细胞和检查信号事件后PS-PSR识别。 此外，我们还将测试胚胎大脑中PS-PSR识别的中断是否会改变胚胎大脑中PS-PSR的表达。 神经前体细胞凋亡。 目的2：我们将研究JNK和经典Wnt/β-catenin信号之间的相互作用， 神经前体细胞自我更新或细胞周期退出的决定。我们将确定是否规范 Wnt/β-连环蛋白通路介导自我更新，以及JNK激活是否减弱经典的Wnt/β-连环蛋白通路。 β-连环蛋白信号传导促进子细胞的分化。 目的3：我们将使用转基因系统来计算成人产生的神经元在大脑中的净增加。 老鼠的大脑此外，我们还将测试β 2受体和FGF 2输注是否能加速成年神经发生。 并吸引新生神经元进入中风受损的大脑区域。 总之，本课题是建立在我们对JNK、磷脂酰丝氨酸受体（PSR）、 经典的Wnt/β-连环蛋白信号转导，重点是调节细胞内信号转导的机制。 神经前体细胞的数量（Aim 1），神经前体细胞退出细胞周期的决定（Aim 2）， 以及脑损伤后神经发生的加速（Aim 3）。这些研究将增进我们对 脑损伤后的神经可塑性和功能恢复。

This proposal is a competitive renewal application for our research program on the role of the Caspase family of proteases, the c-Jun NH2-terminal kinase (JNK), and the phosphatidylserine receptor (PSR) in neuronal apoptosis in brain development and neurological diseases. In the present project, we will extend our research of these signaling pathways with a new emphasis on the mechanism of apoptosis and renewal of neural progenitor cells. Aim 1: We will investigate the mechanism downstream of phosphatidylserine and phosphatidylserine receptor (PS-PSR) recognition leading to the apoptosis of neural progenitor cells. We will express PS on the outer cell surface of neural progenitor cells and examine the signaling events following PS-PSR recognition. In addition, we will test whether the disruption of PS-PSR recognition in the embryonic brain will alter the apoptosis of neural progenitor cells. Aim 2: We will examine the interaction between the JNK and canonical Wnt/beta-catenin signaling in the decision of self-renewal or cell-cycle exit by neural progenitor cells. We will determine whether the canonical Wnt/beta-catenin pathway mediates self-renewal, and whether JNK activation attenuates the canonical Wnt/ beta-catenin signaling to promote differentiation of the daughter cells. Aim 3: We will use a transgenic system to calculate the net increase of adult-generated neurons in the mouse brain. In addition, we will test whether EOF and FGF2 infusion can accelerate adult neurogenesis and attract newly born neurons into stroke damaged brain areas. In summary, the present project is built on our research of JNK, phosphatidylserine receptor (PSR), and canonical Wnt/beta-catenin signaling with an emphasis on the mechanism governing the adjustment of the number of neural progenitor cells (Aim 1), the decision of cell-cycle exit by neural progenitor cells (Aim 2), and the accelerated neurogenesis after brain injury (Aim 3). These studies will enhance our understanding of neural plasticity and functional recovery after brain injury.