Yorkie is required to restrict the injury responses in planarians

PLoS Genet. 2017 Jul 7;13(7):e1006874. doi: 10.1371/journal.pgen.1006874. eCollection 2017 Jul.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Body Patterning / genetics*
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Eye / growth & development
  • Gene Expression Regulation, Developmental
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics*
  • Pharynx / growth & development
  • Planarians / genetics
  • Planarians / growth & development
  • Regeneration / genetics*
  • Signal Transduction
  • Stem Cells / metabolism
  • Tail / growth & development

Substances

  • Nuclear Proteins

Grant support

BJP and AYTL were funded by Ontario Institute for Cancer Research (OICR) Investigator grant #IA-026. AYTL was also funded by The Hospital for Sick Children restracomp PhD award program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.