The planarian neoblast: the rambling history of its origin and some current black boxes.

First described by Randolph in 1897, the nature and main features of planarian neoblasts have a long rambling history. While their morphologically undifferentiated features have long been recognized, their origin and actual role during regeneration have been highly debated. Here I summarize the main stages of this rambling history: 1) undifferentiated, wandering cells of uncertain origin with a main, albeit undefined, role in regeneration (1890-1940s); 2) quiescent, undifferentiated cells whose main function is to build the blastema during regeneration, an idea which culminated in the 'neoblast theory' of the French School (1940-1960); 3) neoblasts as temporal, undifferentiated cells arising by dedifferentiation from differentiated cells (the 'cell dedifferentiation theory'; 1960-1980s); 4) a new paradigm, starting in the late 1970s-early 1980s, that brought together the role of neoblasts as the main cell for regeneration, with its more important role as somatic stem cells for the daily wear and tear of tissues and as the source of germ cells; and 5) more recent developments that culminate in the report of rescuing lethally irradiated planarians by injection of single neoblasts, which makes of neoblasts an unrivaled toti-, pluripotent somatic stem cell system in the Animal Kingdom. I finally discuss some "black boxes" regarding neoblasts which still baffle us, namely their phylogenetic and ontogenetic origins, their role in body size control, how their pool is regulated during growth and degrowth, the logic of their proliferative control, and some 'old' long-sought missing tools.