title: Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration.
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 JAK-STAT, 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 post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration.
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Masahiko
authors.identifier: 0000-0003-3984-4481
authors.initials: M
authors.lastname: Takemura
authors.affiliation: Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA nakat003@umn.edu.
authors.forename: Hiroshi
authors.identifier: 0000-0001-9812-4025
authors.initials: H
authors.lastname: Nakato
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D006497:Heparan Sulfate / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D007422:Intestines / Q000166:cytology*; D053612:Janus Kinases / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D012038:Regeneration / Q000187:drug effects; D050791:STAT Transcription Factors / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013429:Sulfatases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D029721:Drosophila Proteins; D066246:ErbB Receptors; D053823:Hedgehog Proteins; D006497:Heparan Sulfate; D053612:Janus Kinases; D050791:STAT Transcription Factors; D013429:Sulfatases; C568065:SULF1 protein, Drosophila
keywords: Drosophila; Heparan sulfate proteoglycan; Intestine; Regeneration