Control of granule cell poliferation and differentiation

描述(申请人提供)：尽管在以下方面取得了进展 确定调控细胞增殖和分化的因素 颗粒细胞前体(GCP)，这些因素如何发挥它们的影响 细胞周期和分化尚未完全阐明。在这 建议，脑膜信号调制声波刺猬的可能性 (Shh)诱导GCP增殖和垂体腺苷环化酶激活 将研究多肽(PACAP)介导的分化。以工作为基础 提示Myc和CDK-2可能参与Shh诱导的细胞增殖。 这些蛋白质的显性负性形式或其辅助因子将被用于 研究它们在Shh诱导的增殖中的作用。转录因子 已知Gli1、Zic1和Zipro1会影响颗粒细胞的增殖。 这些转录因子的过度表达将与微阵列偶联 分析，以确定对GCP扩散至关重要的途径。已被占用 总之，这些实验将有助于我们对神经的理解。 增殖和分化，将有助于理解临床 髓母细胞瘤等疾病，儿童脑的一种侵袭性形式 癌症，这可能是由于GCP的异常增殖引起的。

DESCRIPTION (provided by applicant): Although progress has been made in identifying factors that regulate the proliferation and differentiation of granule cell precursors (GCPs), how these factors exert their effects on the cell cycle and differentiation have not been fully elucidated. In this proposal, the possibility that meningeal signals modulate Sonic hedgehog (Shh)-induced GCP proliferation and pituitary adenylate cyclase activating peptide (PACAP)-mediated differentiation will be examined. Building on work that suggests that Myc and CDK 2 may participate in Shh-induced proliferation, dominant negative forms of these proteins or their co-factors will be used to investigate their role in Shh-induced proliferation. The transcription factors Gli1, Zic1, and Zipro1 are known to influence granule cell proliferation. Overexpression of these transcription factors will be coupled with microarray analysis in order to identify pathways important to GCP proliferation. Taken together, these experiments will contribute to our understanding of neural proliferation and differentiation, and will aid in understanding clinical disorders such as medulloblastoma, an aggressive form of pediatric brain cancer, that may arise from the dysregulated proliferation of GCPs.