涡虫作为理想的干细胞和神经再生研究模式生物，能够依靠体内大量的成体干细胞，再生出完整的头部和整个神经系统，其神经再生过程涉及多种信号通路的调控，尤其TGF-β/Smads信号通路可能起着重要调控作用，但调控机制尚未阐明。我们研究发现TGF-β/Smads信号通路上Djsmad-4基因在再生过程中具有显著差异表达，敲低后可显著阻断涡虫再生，且神经系统再生发生异常；原位杂交结果显示Djsmad-4在再生过程中表达于干细胞富集的胚基处，提示TGF-β/Smads信号通路可能通过调控涡虫干细胞增殖、分化，影响神经系统的再生，最终导致再生异常。本研究正是基于上述假说，拟通过RNA干扰、差异转录组分析、原位杂交、免疫荧光等多种方法研究Djsmad-4及其下游调控基因的功能，初步阐明TGF-β/Smads信号通路调控涡虫干细胞增殖与分化，以及神经再生的分子机制。

The planarian is an ideal model organism to study stem cell and neural regeneration. It contains a high number of adult stem cells and could regenerate the whole head and nervous system. The regeneration process involves multiple signaling pathways including the TGF-β/Smads signaling pathway which may play an important role in the regulation of regeneration. However, the underlying mechanism remains unclear. In our study, the Dugesia japonica Smad-4 (Djsmad-4), a core component of TGF-β/Smads signaling pathway, showed different expression patterns in normal and regenerate tissues. The Djsmad4(RNAi) animals failed to regenerate, and produced an abnormal nervous system. The in-situ hybridization revealed that the Djsmad-4 expressed in blastemas where the stem cells enriched. These results suggested the TGF-β/Smads signaling pathway may result in abnormal regeneration by regulating the proliferation and differentiation of the stem cells. Based on the above information, we will investigate the function of Djsmad-4 and its downstream genes with RNAi, comparative transcriptomics, in-situ hybridization and immunofluorescence methods, to reveal the the possible mechanism of TGF-β/Smads signaling pathway in the regulation of the proliferation and differentiation of the stem cells, as well as the regeneration of the nervous system.