Planarian EGF repeat-containing genes megf6 and hemicentin are required to restrict the stem cell compartment

PLoS Genet. 2020 Feb 20;16(2):e1008613. doi: 10.1371/journal.pgen.1008613. eCollection 2020 Feb.

Abstract

The extracellular matrix (ECM) is important for maintaining the boundaries between tissues. This role is particularly critical in the stem cell niche, as pre-neoplastic or cancerous stem cells must pass these boundaries in order to invade into the surrounding tissue. Here, we examine the role of the ECM as a regulator of the stem cell compartment in the planarian Schmidtea mediterranea, a highly regenerative, long-lived organism with a large population of adult stem cells. We identify two EGF repeat-containing genes, megf6 and hemicentin, with identical knockdown phenotypes. We find that megf6 and hemicentin are needed to maintain the structure of the basal lamina, and in the absence of either gene, pluripotent stem cells migrate ectopically outside of their compartment and hyper-proliferate, causing lesions in the body wall muscle. These muscle lesions and ectopic stem cells are also associated with ectopic gut branches, which protrude from the normal gut towards the dorsal side of the animal. Interestingly, both megf6 and hemicentin knockdown worms are capable of regenerating tissue free of both muscle lesions and ectopic cells, indicating that these genes are dispensable for regeneration. These results provide insight into the role of planarian ECM in restricting the stem cell compartment, and suggest that signals within the compartment may act to suppress stem cell hyperproliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult Stem Cells / physiology*
  • Animals
  • Animals, Genetically Modified
  • Cell Movement / genetics
  • Extracellular Matrix / metabolism
  • Gene Knockdown Techniques
  • Genes, Helminth / physiology*
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Platyhelminths / cytology
  • Platyhelminths / physiology*
  • Pluripotent Stem Cells / physiology*
  • Regeneration / genetics
  • Stem Cell Niche / genetics*

Substances

  • Helminth Proteins

Grants and funding