CommentaryThe freshwater planarian Schmidtea mediterranea: embryogenesis, stem cells and regeneration
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.
Section snippets
Are planarians lophotrochozoans?
Planarians, are members of the phylum Platyhelminthes, and share with vertebrates key traits such as bilateral symmetry, three germ layers — ectoderm, mesoderm and endoderm — and dorsoventral and anteroposterior polarities. Planarians are also among the simplest bilaterians to display cephalization — that is, a complex and well-organized accumulation of neurons in their anterior region. These characteristics have attracted the attention of a long succession of zoologists, and the taxonomic
If not by spiral cleavage, how do the embryos of freshwater planarians develop?
Although much is known about the embryogenesis of other orders of flatworms such as the marine polyclads [34] and the acoels 35., 36., little contemporary work has been done on the embryos of freshwater planarians 37., 38., 39.. To my knowledge, the last detailed studies of the highly derived embryogenesis of freshwater planarians were carried out by Metschnikoff (1883) [40], Ijima (1884) [41], Hallez (1887) [42], Korschelt and Heider (1895) [43], Mattiesen (1904) [44], and Fulinski (1916) [45]
The embryos of Schmidtea mediterranea are accessible to molecular studies
To learn more about the embryogenesis of freshwater planarians, it is necessary to have ready access to large numbers of embryos and to develop the necessary techniques to study them at the molecular and cellular level. To accomplish this task, my laboratory has chosen to develop S. mediterranea as a species in which to carry out embryological and molecular developmental studies. There are several advantages to using S. mediterranea over other freshwater planarians, and these have been
Bilaterian development, regeneration and the embryos of Schmidtea mediterranea
As counterintuitive as it may sound, studying the highly modified embryogenesis of freshwater planarians is bound to expand our understanding of common regulatory processes operating during bilaterian development. By determining the molecular events leading to cell-determination and differentiation in the ectolecithal embryos of S. mediterranea (Figure 2), it should be possible to recognize plesiomorphic bilaterian features shared by the ecdysozoans, lophotrochozoans and deuterostomes. Such
Embryogenesis and the planarian stem cells
Any future studies of freshwater planarian embryogenesis will need to address the mechanism by which neoblasts arise during development, as these totipotent cells are maintained in the soma of the adult organism and give rise, post-embryonically, to the germ line. Neoblasts, therefore, embody a fundamental difference between the ontogeny of somatic and germ tissues in planarians and the ecdysozoa. For example, other than the gonads, the somatic tissues of flies and nematodes are entirely
Conclusions
The molecular and genomic revolutions have greatly enhanced our understanding of ecdysozoan and deuterostome genetics and development. The same, however, cannot be said of the non-ecdysozoan protostomes. Because of the evolutionary distance of flatworms from ecdysozoans and deuterostomes (Figure 1), the biology of S. mediterranea merits a closer look. Studying a non-ecdysozoan such as S. mediterranea in which gene function can be tested will facilitate comparative evolutionary and developmental
Update
Mineta et al. [54] have utilized a collection of ∼3000 expressed sequence tags obtained from a close relative of S. mediterranea (Dugesia japonica) to investigate the evolutionary origins of the bilaterian central nervous system. From this collection of cDNAs, the authors identified 116 nervous-system related genes. Six of these genes were absent in C. elegans and/or Drosophila, yet all 116 planarian genes were represented in the Homo sapiens orfeome. These and other data allowed Mineta et al.
Acknowledgements
I would like to extend my thanks to Peter W Reddien and Tatjana Piotrowski for critical reading of this manuscript, and to Maria Pala for her kind gift of the wild-type sexual strain of Schmidtea mediterranea. This work was supported by grant RO-1 GM57260 from the National Institutes of Health, National Institute of General Medical Sciences to A Sánchez Alvarado.
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