The respective roles of mitotic activity and of cell differentiation in planarian regeneration.

Blastema formation, which is the first step of regeneration in adult Metazoa, is generally considered to be merely an accumulation of undifferentiated cells provided by mitotic activity, which occurs near the wound following amputation. Afterwards, these undifferentiated cells are thought to differentiate rapidly, thus affecting the organization of the regenerate. Some authors have postulated that a close similarity exists between these undifferentiated cells and the blastomeres of a young embryo, and that the influence exercised by the stump tissues in blastema differentiation is a typical inductive process. This concept would imply two successive steps in regeneration: (1) blastema formation, exclusively dependent upon mitotic activity, even after the previous accumulation of undifferentiated cells resulting from migration (Dubois, 1949), (2) the transformation of the blastema into a regenerate as differentiation occurs. Up to now, the first step seemed to be confirmed by experiment, since some authors have observed that some experimental factors which prevent regeneration (X-rays and mitoclastic poisons) inhibit mitoses. However, it has not yet been possible to produce any evidence of the occurrence of a completely undifferentiated state in the blastema. As soon as it has grown large enough to be surgically separated from the old tissues, it is already fully determined (Sengel, 1960). Experiments carried out in our laboratory have shown repeatedly that mitotic activity is not the determinant factor in regeneration. Indeed, a high mitotic activity does not necessarily cause blastema formation, and blastema formation is sometimes possible when mitoses are inhibited. The first morphological manifestation of regeneration probably follows the onset of cell differentiation in the undifferentiated material.