Role of c-Jun N-terminal kinase activation in blastema formation during planarian regeneration
Article first published online: 30 MAR 2011
© 2011 The Authors. Journal compilation © 2011 Japanese Society of Developmental Biologists
Development, Growth & Differentiation
Volume 53, Issue 3, pages 389–400, April 2011
How to Cite
Tasaki, J., Shibata, N., Sakurai, T., Agata, K. and Umesono, Y. (2011), Role of c-Jun N-terminal kinase activation in blastema formation during planarian regeneration. Development, Growth & Differentiation, 53: 389–400. doi: 10.1111/j.1440-169X.2011.01254.x
- Issue published online: 15 APR 2011
- Article first published online: 30 MAR 2011
- Received 22 November 2010; revised 21 December 2010; accepted 21 December 2010.
- cell cycle;
- c-Jun N-terminal kinase;
- stem cell
The robust regenerative abilities of planarians absolutely depend on a unique population of pluripotent stem cells called neoblasts, which are the only mitotic somatic cells in adult planarians and are responsible for blastema formation after amputation. Little is known about the molecular mechanisms that drive blastema formation during planarian regeneration. Here we found that treatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125 blocked the entry of neoblasts into the M-phase of the cell cycle, while allowing neoblasts to successfully enter S-phase in the planarian Dugesia japonica. The rapid and efficient blockage of neoblast mitosis by treatment with the JNK inhibitor provided a method to assess whether temporally regulated cell cycle activation drives blastema formation during planarian regeneration. In the early phase of blastema formation, activated JNK was detected prominently in a mitotic region (the “postblastema”) proximal to the blastema region. Furthermore, we demonstrated that undifferentiated mitotic neoblasts in the postblastema showed highly activated JNK at the single cell level. JNK inhibition by treatment with SP600125 during this period caused a severe defect of blastema formation, which accorded with a drastic decrease of mitotic neoblasts in regenerating animals. By contrast, these animals still retained many undifferentiated neoblasts near the amputation stump. These findings suggest that JNK signaling plays a crucial role in feeding into the blastema neoblasts for differentiation by regulating the G2/M transition in the cell cycle during planarian regeneration.