Reactivating head regrowth in a regeneration-deficient planarian species

• Published in: Nature (London) Vol. 500; no. 7460; pp. 81 - 84
• Main Authors: Liu, S.-Y., Selck, C., Friedrich, B., Lutz, R., Vila-Farré, M., Dahl, A., Brandl, H., Lakshmanaperumal, N., Henry, I., Rink, J. C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2013; Nature Publishing Group
• Subjects: 631/136; Amputation; Animals; beta Catenin - biosynthesis; beta Catenin - deficiency; beta Catenin - genetics; beta Catenin - metabolism; Body Patterning; Cloning; Comparative studies; Defects; Experiments; Genes; Genetic engineering; Head - growth & development; Head - physiology; Histology; Humanities and Social Sciences; Hybridization; letter; Ligands; Models, Animal; Molecular Sequence Data; multidisciplinary; Physiological aspects; Planarians - anatomy & histology; Planarians - physiology; Platyhelminthes; Regeneration; Regeneration (Biology); Regrowth; Science; Tail - growth & development; Wnt Proteins - metabolism; Wnt Signaling Pathway
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature12414

Although the capacity for tissue regeneration of planarians is exceptional, planarians with more limited regenerative capacities are known; here knocking down components of the Wnt signalling pathway rescues head regeneration in the regeneration-impaired planarian Dendrocoelum lacteum , revealing that manipulating a single signalling pathway can reverse the evolutionary loss of regenerative potential. Controlling planarian regeneration capacity Planarians are flatworms common in streams and ponds whose capacity for tissue regeneration is legendary. But with more limited regenerative capacities are known. Three papers published in Nature this week study Planaria with differing regenerative capacities and identify the Wnt/β-catenin molecular signalling pathway, important in embryonic development and adult homeostasis in multicellular organisms, as central to the regeneration mechanism. Yoshihiko Umesono et al . identify ERK and β-catenin signalling as the basis for a morphogenetic gradient along the anterior–posterior axis that is required for regeneration. These authors also demonstrate that inhibition of β-catenin can rescue head regeneration in Phagocata kawakatsui , a planarian that otherwise cannot regenerate heads from the posterior pieces. James Sikes and Phillip Newmark show in Procotyla fluviatilis , which has restricted ability to replace missing tissues, that Wnt signalling is aberrantly regulated in regeneration-deficient tissues. Downregulation of Wnt signalling in these regions restores regenerative abilities, including the formation of blastemas and even new heads. Jochen Rink and colleagues show that in the otherwise regeneration-incompetent Dendrocoelum lacteum , knockdown of components in the Wnt signalling pathway introduces the ability to regenerate lost tissues. Species capable of regenerating lost body parts occur throughout the animal kingdom, yet close relatives are often regeneration incompetent 1 , 2 . Why in the face of ‘survival of the fittest’ some animals regenerate but others do not remains a fascinating question 3 . Planarian flatworms are well known and studied for their ability to regenerate from minute tissue pieces, yet species with limited regeneration abilities have been described even amongst planarians 4 . Here we report the characterization of the regeneration defect in the planarian Dendrocoelum lacteum and its successful rescue. Tissue fragments cut from the posterior half of the body of this species are unable to regenerate a head and ultimately die 5 . We find that this defect originates during the early stages of head specification, which require inhibition of canonical Wnt signalling in other planarian species 6 , 7 , 8 . Notably, RNA interference (RNAi)-mediated knockdown of Dlac-β-catenin-1 , the Wnt signal transducer, restored the regeneration of fully functional heads on tail pieces, rescuing D. lacteum ’s regeneration defect. Our results demonstrate the utility of comparative studies towards the reactivation of regenerative abilities in regeneration-deficient animals. Furthermore, the availability of D. lacteum as a regeneration-impaired planarian model species provides a first step towards elucidating the evolutionary mechanisms that ultimately determine why some animals regenerate and others do not.