Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration

Masahiko Takemura, Hiroshi Nakato

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAKSTAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that posttranscriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration.

Original languageEnglish (US)
Pages (from-to)332-343
Number of pages12
JournalJournal of cell science
Volume130
Issue number2
DOIs
StatePublished - Jan 1 2017

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Keywords

  • Drosophila
  • Heparan sulfate proteoglycan
  • Intestine
  • Regeneration

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