The freshwater planarian Schmidtea mediterranea: embryogenesis, stem cells and regeneration

Abstract

Planarians have been used as a model to study development and regeneration for more than 200 years. Research on these animals has traditionally focused on surgical and pharmacological manipulations. Recently, the dissection of planarians has become more molecular in nature. The isolation of thousands of expressed sequence tags and the introduction of in situ hybridizations, immunocytology, and RNA-mediated gene interference has opened the door to gene discovery and to the study of gene function in planarians during development and regeneration. These advances promise to shed mechanistic insight into basic biological attributes such as regeneration and stem-cell regulation.

Introduction

It is not generally known that before TH Morgan became indissolubly associated with Drosophila melanogaster, he produced a notable body of work on planarians (flatworms). From 1898 to1905, Morgan wrote a dozen incisive papers dealing with the biology of these organisms 1., 2., 3., 4., 5., 6., 7., 8., 9., 10., 11., 12.. It is not too difficult to imagine how an animal that can regenerate complete individuals from minuscule body parts 1., 13., and that possesses the uncanny ability to grow and ‘de-grow’ depending on food availability 14., 15., 16., 17., 18., 19. could have so thoroughly intrigued and puzzled Morgan [20].

Planarians are, indeed, fascinating animals and in recent years, research on these organisms has begun to move away from mostly surgical and pharmacological studies into the realm of molecular biology and functional genomics 21., 22.. The motivation for this significant methodological expansion is the same as it has been for over 200 years: to better understand the extraordinary biological attributes of planarians and to expand our knowledge of metazoan biology. For example, a small fragment removed from either flank of a planarian is capable of re-specifying its body midline to regain bilateral symmetry, while simultaneously preserving anteroposterior and dorsoventral polarities and resetting these axes to their appropriate positional values 1., 23.. How this is accomplished is still not understood. Such plasticity illustrates the enormous capacity possessed by adult planarians to both maintain and regulate the form and function of their body and is in direct contrast with the rigidity displayed by the adult forms of other popular invertebrate model systems such as the fruitfly (Drosophila melanogaster) and the nematode worm (Caenorhabditis elegans).

The source of the plasticity and regenerative abilities of planarians is a dynamic population of adult, totipotent, somatic stem cells known as neoblasts. Neoblasts are attention grabbers: they are the only mitotically active cells in adult planarians and are capable of giving rise to all the cell types found in this organism 24., 25., 26., including the germ line [4]. The totipotentiality of the soma became patently clear to Morgan, who in 1902 observed how a planarian head fragment lacking any vestiges of the reproductive system could regenerate not only the missing trunk and tail, but also functional gonads from somatic tissues [4]. In other words, unlike Drosophila and C. elegans, planarians do not appear to segregate their germ-cell lineage during embryogenesis. The ability of neoblasts to generate both somatic and germ-cell lineages in adult tissues poses absorbing and still unanswered questions about the mechanisms by which totipotentiality and fate restriction are regulated in planarians.

In this Commentary, I discuss how the study of these and other planarian attributes are likely to complement and expand on current developmental biology research. I will also argue for the use of a particular species, namely Schmidtea mediterranea, to standardize these studies. Research into the developmental processes that are particularly accessible in the flatworm such as regeneration and stem cell activity will provide crucial insight into metazoan evolution, development, and the genetic mechanisms that generate diversity.