sil1是目前唯一发现的Marinesco-Sjgren综合症的致病基因，智力发育障碍是该病主要特征，提示SIL1在中枢发育中发挥重要功能，但是目前机制不明。最新研究显示，SIL1作为内质网分子伴侣蛋白，具有细胞表达特异性和底物特异性，尤其是在神经系统发挥重要功能。在我们的前期研究中，我们发现沉默sil1基因会影响Reelin信号通路，使其下游分子Dab1的磷酸化水平显著降低。此外，受其影响，NMDA受体特定亚型的发育表达被抑制。这些结果提示，SIL1可能参与了一系列中枢发育相关蛋白的表达调控。在本课题中，我们将在细胞分子、胚胎、整体三个层次，使用分子细胞、胚胎电转、转基因、行为学等多种实验手段，以SIL1和Reelin、NMDA受体的相互作用机制为切入点，探索SIL1在中枢皮层发育过程中的作用及分子机制，开辟从底物特异性内质网分子伴侣蛋白为切入点，探索中枢发育调控机制的新视角。

The sil1 gene, which encodes the SIL1 protein, is the only causal gene of Marinesco-Sjgren syndrome (MSS). 90% of MSS patients show moderate to severe mental retardation. It is not clear why function deficiency of SIL1 will cause mental retardation. SIL1 is the co-factor of the Endoplasmic Reticulum(ER) chaperone Bip. SIL1 cooperates with Bip to help nascent protein folding and assembly. Recent researches have shown that SIL1 may play important functions in central nervous system. A recent research showed the function of SIL1 in regulating the development of the central nervous system, in which silencing of SIL1 caused abnormal neuronal migration and morphology during corticogenesis and this may be the cause of mental retardation during MSS. However the molecular mechanism of SIL1 regulating central development is still unclear. We found in our experiment that the Reelin signaling pathway, which plays vital roles in corticogenesis, was impaired after silencing of SIL1. The expression of both receptors of Reelin, ApoeR2 and VLDLR, were significantly reduced, as well as the phosphorylation level of a key molecule of Reelin signaling pathway, Dab1. And as a result the expression of GluN2A-containing NMDA receptor was inhibited during central development. These results suggested that SIL1 may be involved in regulating corticogenesis through Reelin signal pathway. And also these results implicated that SIL1 may selectively regulate the expression of a series of central development related protein. In this project, we plan to focus on this hypothesis and to underpin the mechanism of SIL1 in regulating central development. And further more we want to propose a new study scope that the ER chaperone protein may modulate particular function of contral nervous system through their substrate specificity.