DAPT (N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester) is a γ-secretase inhibitor that indirectly blocks the activity of Notch pathway. It is a potential therapeutic target drug for many diseases, such as cancer, neurological, cardiovascular, and cerebrovascular diseases. However, the pharmacological action and specific mechanisms of DAPT are not clear. Planarians have strong regenerative capacity and can regenerate a new individual with a complete nervous system in one week. Thus, they are used as an ideal indicator of environmental toxicants and a novel model for studying neurodevelopmental toxicology. In this study, different concentrations and treatment times of DAPT are used to analyze the gene expression levels of major components in Notch pathway. The results show that the optimal concentration and exposure time of DAPT is 100 nM for 10 days in planarians and indicate that the inhibitory of DAPT treatment on Notch pathway is time- and concentration-dependent. The potential impact of DAPT is effectively analyzed by qPCR, WISH, and Immunofluorescence. The results indicate that DAPT exposure causes intact planarian wavy or swollen, and regenerative planarians asymmetric growth or muti-eye. Moreover, DAPT exposure increases cell proliferation and apoptosis, results in neurodevelopmental defects and dynamic changes of some marker genes. These results suggest that the balance of proliferation and apoptosis is disturbed, and then, affecting tissue homeostasis and differentiation. These findings demonstrate that DAPT has serious side effects in organisms and relies on Notch pathway to determine cell fate, it is cautious in the use of DAPT as a potential therapeutic approach for the disease in clinical trials.

DAPT（N- [ N-（3，5-二氟苯乙酰基）-1-丙氨酰基] -s-苯基甘氨酸丁酯）是一种γ-分泌酶抑制剂，可间接阻断Notch途径的活性。它是许多疾病（例如癌症，神经系统疾病，心血管疾病和脑血管疾病）的潜在治疗靶标药物。但是，DAPT的药理作用和具体机制尚不清楚。浮游生物具有很强的再生能力，可以在一个星期内再生出具有完整神经系统的新个体。因此，它们被用作环境毒物的理想指示剂和研究神经发育毒理学的新型模型。在这项研究中，使用不同浓度和不同时间的DAPT来分析Notch途径中主要成分的基因表达水平。结果表明，DAPT的最佳浓度和暴露时间为100 nM，持续10天，表明在Notch途径对DAPT的抑制作用与时间和浓度有关。通过qPCR，WISH和免疫荧光可以有效地分析DAPT的潜在影响。结果表明，DAPT暴露会导致完整的涡虫波状或肿胀，以及再生涡虫的不对称生长或多眼。此外，DAPT暴露会增加细胞增殖和凋亡，导致神经发育缺陷和某些标记基因的动态变化。这些结果表明，增殖和凋亡的平衡被破坏，进而影响组织的稳态和分化。