Regenerative responses following DNA damage - β-Catenin mediates head regrowth in the planarian Schmidtea mediterranea

Annelies Wouters, Jan Pieter Ploem, Sabine A.S. Langie, Tom Artois, Aziz Aboobaker, Karen Smeets*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Pluripotent stem cells hold great potential for regenerative medicine. Increased replication and division, such is the case during regeneration, concomitantly increases the risk of adverse outcomes through the acquisition of mutations. Seeking for driving mechanisms of such outcomes, we challenged a pluripotent stem cell system during the tightly controlled regeneration process in the planarian Schmidtea mediterranea. Exposure to the genotoxic compound methyl methanesulfonate (MMS) revealed that despite a similar DNAdamaging effect along the anteroposterior axis of intact animals, responses differed between anterior and posterior fragments after amputation. Stem cell proliferation and differentiation proceeded successfully in the amputated heads, leading to regeneration of missing tissues. Stem cells in the amputated tails showed decreased proliferation and differentiation capacity. As a result, tails could not regenerate. Interference with the body-axis-associated component β-catenin-1 increased regenerative success in tail fragments by stimulating proliferation at an early time point. Our results suggest that differences in the Wnt signalling gradient along the body axis modulate stem cell responses to MMS.

Original languageEnglish
Article numberjcs237545
JournalJournal of Cell Science
Volume133
Issue number8
DOIs
Publication statusPublished - Apr 2020
Externally publishedYes

Keywords

  • DNA damage
  • Planarian
  • Regeneration
  • Stem cell
  • β-catenin

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