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About the Authors:
Alexander Y. T. Lin
Affiliations Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
Bret J. Pearson
* E-mail: [email protected]
Affiliations Hospital for Sick Children, Program in Developmental and Stem Cell Biology, Toronto, ON, Canada, Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada, Ontario Institute for Cancer Research, Toronto, ON, Canada
ORCID http://orcid.org/0000-0002-3473-901XAbstract
Regeneration requires the precise integration of cues that initiate proliferation, direct differentiation, and ultimately re-pattern tissues to the proper size and scale. Yet how these processes are integrated with wounding responses remains relatively unknown. The freshwater planarian, Schmidtea mediterranea, is an ideal model to study the stereotyped proliferative and transcriptional responses to injury due to its high capacity for regeneration. Here, we characterize the effector of the Hippo signalling cascade, yorkie, during planarian regeneration and its role in restricting early injury responses. In yki(RNAi) regenerating animals, wound responses are hyper-activated such that both stem cell proliferation and the transcriptional wound response program are heighted and prolonged. Using this observation, we also uncovered novel wound-induced genes by RNAseq that were de-repressed in yki(RNAi) animals compared with controls. Additionally, we show that yki(RNAi) animals have expanded epidermal and muscle cell populations, which we hypothesize are the increased sources of wound-induced genes. Finally, we show that in yki(RNAi) animals, the sensing of the size of an injury by eyes or the pharynx is not appropriate, and the brain, gut, and midline cannot remodel or scale correctly to the size of the regenerating fragment. Taken together, our results suggest that yki functions as a key molecule that can integrate multiple aspects of the injury response including proliferation, apoptosis, injury-induced transcription, and patterning.
Author summary
The planarian displays a remarkable ability to regenerate any tissue from mere fragments of its original size. This high capacity to regenerate is attributed to the abundant population of pluripotent adult stem cells. In response to an injury, such as an amputation, stem cells proliferate and replace the lost tissues de novo (epimorphosis), whereas existing tissue must rescale to the correct proportions in relation to the new fragment size (morphallaxis). Currently, the molecules that control either the responses to injury or the...