髓母细胞瘤是最常见的儿童恶性脑肿瘤，虽然结合手术和放化疗，仍有30%的患者无法被治愈。因此亟需对髓母细胞瘤的发生发展机制进行更深入彻底的研究，以解决临床治疗手段不够特异高效的问题。本研究在预实验中发现髓母细胞瘤形成过程中伴随着星形胶质细胞的积聚，敲除星形胶质细胞显著降低了肿瘤发展，并且肿瘤中的星形胶质细胞分泌Shh配体，而外源Shh能够在体外促进髓母细胞瘤细胞的大量增殖。基于以上发现我们推测星形胶质细胞通过分泌Shh配体促进髓母细胞瘤的发展。本课题拟采用条件性基因敲除小鼠来建立髓母细胞瘤模型，并通过分子生物学和流式细胞术等方法来研究髓母细胞瘤中星形胶质细胞和Shh配体的相关性，确证星形胶质细胞和其分泌的Shh配体在肿瘤发展中的重要作用，同时阐述Shh促进髓母细胞瘤发展的具体信号通路是通过结合Ptch2介导的。本研究将从新的视角阐述髓母细胞瘤的形成机制，为髓母细胞瘤的防治提供新靶点。

Medulloblastoma (MB) is the most common malignant brain tumor in children. Approximately one third of MB patients remain incurable despite aggressive multi-modality standard therapies. There’s an urgent need to develop more specific and effective treatment strategies with low side effects and low resistance. In our preliminary studies, we found that astrocytes accumulate in the MB tumor tissue and ablation of them significantly inhibit the progression of MB. Also, astrocytes in MB produce Shh ligand; furthermore, extrogenous Shh promotes the proliferation of MB cells in vitro. Thus, we hypothesize that tumor associated astrocytes promote MB progression through secreting Shh ligand. To verify our hypothesis, we will utilize the transgenic mice in which Shh is specifically deficient in astrocytes to generate MB model, and determine whether the Shh secreted by astrocytes contributes to the MB progression. We will further investigate whether Ptch2 mediates MB cells proliferation in response to the astrocytes derived Shh. Our study is aimed to evaluate the contribution of astrocytes in MB and to investigate the novel mechanism of MB progression. Our study would be beneficial for developing improved strategies to treat MB.