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

Abstract

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. KEY WORDS: planarian, neoblast, totipotency, dedifferentiation, stem cell A general overview of cell potency during developmentThe developmental potential of cells within embryos, and by extension in adult organisms has been one of the biggest riddles in Developmental Biology. A large amount of observations and experiments soon made clear that egg cells and early blastomeres in most phyla are totipotent cells (cells able to give rise to all cell types including germ cells). It also became evident that as development goes on, such potentialities, however ample, become restricted. After the morula stage in mammals, cells of the inner cell mass and from the outer trophoblasts are no longer totipotent but pluripotent (able to give rise to cell types of all three germ layers or to the placenta, respectively). Later, embryonic germ layers segregate. Embryonic outer cells (ectoderm), give rise to several epidermal derivatives together with central nervous system and neural crest cell types but not to any embryonic inner cells, or endoderm derivatives, and vice versa. Such cells are considered multipotent (able to give rise to several cell types). The final stage, the adult Int. J. Dev. Biol. 56: [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] doi: 10.1387/ijdb.113463jb organism, is formed of thousands, millions, billions, or trillions of cells of different types (over 200-300 in complex vertebrates) patter...

Specialized progenitors and regeneration

“…Planarian regeneration requires a population of proliferative cells, called neoblasts, which have been studied for over a century (Keller, 1894;Baguñà, 2012). Not only do planarians regenerate, but adult animals also constantly replace aged differentiated cells.…”

Genome and transcriptome of the regeneration-competent flatworm, Macrostomum lignano

“…This regenerative capacity is thought to be attributable to the presence of somatic stem cells, termed neoblasts (10,11). In Schmidtea mediterranea (planarian flatworm), even a single transplanted neoblast has the ability to rescue, regenerate, and change the genotype of a fatally irradiated worm (12).…”

Genome-wide analysis of the bHLH gene family in planarians identifies factors required for adult neurogenesis and neuronal regeneration

“…Following amputation, planarians are capable of restoring lost body parts from a population of adult pluripotent stem cells called neoblasts (Baguñà, 2012;Elliott and Sánchez Alvarado, 2013). Planarian stem cells share conserved pluripotency determinants with mammalian stem cells (Labbé et al, 2012;Önal et al, 2012;Solana et al, 2012) and serve to replace cells lost during normal physiological cell turnover or after amputation.…”