Migratory regulation by MTA homologous genes is essential for the uniform distribution of planarian adult pluripotent stem cells.

Abstract

The migration of adult stem cells in vivo is an important issue, but the complex tissue structures involved, and limited accessibility of the cells hinder a detailed investigation. To overcome these problems, the freshwater planarian Dugesia japonica was used because it has a simple body plan and abundant adult pluripotent stem cells (neoblasts) distributed uniformly throughout its body. To investigate the migratory mechanisms of neoblasts, two planarian homologous genes of metastatic tumor antigen (MTA-A and MTA-B), a protein involved in cancer metastasis that functions through histone deacetylation, were identified, and their function was analyzed using RNA interference (RNAi). MTA-A or MTA-B knockdown disrupted homeostatic tissue turnover and regeneration in planarians. Whereas neoblasts in MTA-A (RNAi) and MTA-B (RNAi) animals were maintained, neoblast differentiation was inhibited. Furthermore, the normal uniform neoblast distribution pattern changed to a branch-like pattern in MTA-A (RNAi) and MTA-B (RNAi) animals. To examine the neoblast migratory ability, a partial X-ray irradiation assay was performed in D. japonica. Using this assay system, the MTA-A knockdown neoblasts migrated collectively in a branch-like pattern, and the MTA-B knockdown neoblasts were not able to migrate. These results indicated that MTA-A was required for the exit of neoblasts from the branch-like region, and that MTA-B was required for neoblast migration. Thus, the migration mediated by MTA-A and MTA-B enabled uniform neoblast distribution and was required for neoblast differentiation to achieve tissue homeostasis and regeneration.