REGENERATION AND PATTERN-FORMATION IN PLANARIANS - CELLS, MOLECULES AND GENES

The process of regeneration in freshwater planarians (Platyhelminthes; Turbellaria; Tricladida) is reviewed. Long-standing questions such as time and role of wound healing, the origin of blastema cells and the time and mode of determination of lost structures have come to be solv ed in recent years due to the use of old and new cell labelling and tr ansplantation methods. In most turbellarian species wound healing occu rs in less than 1 hour. Sound evidence has been produced to support th e origin of blastema cells from undifferentiated stem-cells or neoblas ts, and determination of lost structures takes place during the first two days of regeneration following a disto-proximal sequence. These re sults suggest that epithelial-mesenchymal interactions, brought up by wound healing, may be instrumental, through cell-cell interactions or activating transient morphogenetic gradients, in setting the early pat tern of lost structures upon the equivalent blastema and postblastema cells. We are fully ignorant, however, on the molecular nature of subs tances playing such roles as well as on how positional information alo ng the antero-posterior and dorso-ventral axes is set and maintained i n the intact organism and reset again and transmitted to blastema cell s in regenerating organisms. Molecular biology and recombinant DNA tec hniques brought into the field of planarian regeneration in the last 1 0 years have opened new research perspectives but produced limited res ults. As expected, signals, receptors and transducing molecules which activate cell proliferation and differentiation in planarians were fou nd to be not different to those known to operate in other activated sy stems. Instead, monoclonal antibodies (mAbs) against positional specif ic antigens have recently been obtained and found to be very sensitive to changes in positional values during regeneration. Homeobox contain ing genes, namely those belonging to the HOM/Hox Antennapedia class ha ve been detected and sequenced in different species. Whether or not th ey are clustered in the genome, how are they expressed along the anter o-posterior body axis in both intact and regenerating organisms, and h ow are they linked to the positional markers detected by mAbs are key questions to answer and a matter of intense research. Finally, the rec ent finding of active transposable elements in some species of planari ans opens the way to obtain transformed neoblasts and, ultimately, tra nsgenic planarians. When available, this would represent an extremely useful tool to study cell lineage, as well as to test the function of cloned genes and to induce loss and gain of function mutations. Based on these results and perspectives, a new research agenda is suggested.