Myogenic differentiation of Drosophila Schneider cells by DNA double-strand break-inducing drugs.

Drosophila melanogaster has been widely used as a model organism to study various aspects of development. Apart from the whole Drosophila embryo, there are a number of cultured cell lines derived from Drosophila embryo that have also been used for elucidating various aspects of development. Drosophila Schneider line 2 cells were derived from the late stages of the embryo (Schneider, 1972). We found that the Schneider cells undergo myogenic differentiation upon treatment with neocarzinostatin (NCS), DNA double-strand break (DSB)-inducing drug, as indicated by elongated morphology, myosin heavy chain protein expression, multinucleation and exit from the cell cycle. No induction of differentiation was observed when cell proliferation was inhibited with drugs that do not cause DNA DSBs. Pre-treatment of Schneider cells with inhibitors of PKC, PP 1/2A, p38 MAPK, JNK and proteasomes resulted in the inhibition of morphological differentiation induced by NCS. These results indicate that DNA DSBs can turn on the myogenic program in Drosophila Schneider cells and the process is dependent on PK C-, PP 1/2A-, p38 MAPK-, and JNK- mediated signaling and proteasomal activity. The molting hormone, 20-hydroxyecdysone (20-HE), also showed an anti-myogenic effect on the process. This is the first report of insect cells undergoing differentiation by DNA DSB-inducing drugs as far as we know, and it provides a very useful and convenient in vitro system to study various aspects of Drosophila myogenesis.