Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells

Alla Amcheslavsky, Naoto Ito, Jin Jiang, Y. Tony Ip

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Intestinal stem cells (ISCs) in the adult Drosophila melanogaster midgut can respond to damage and support repair. We demonstrate in this paper that the tuberous sclerosis complex (TSC) plays a critical role in balancing ISC growth and division. Previous studies have shown that imaginal disc cells that are mutant for TSC have increased rates of growth and division. However, we report in this paper that loss of TSC in the adult Drosophila midgut results in the formation of much larger ISCs that have halted cell division. These mutant ISCs expressed proper stem cell markers, did not differentiate, and had defects in multiple steps of the cell cycle. Slowing the growth by feeding rapamycin or reducing Myc was sufficient to rescue the division defect. The TSC mutant guts had a thinner epithelial structure than wild-type tissues, and the mutant flies were more susceptible to tissue damage. Therefore, we have uncovered a context-dependent phenotype of TSC mutants in adult ISCs, such that the excessive growth leads to inhibition of division.

Original languageEnglish (US)
Pages (from-to)695-710
Number of pages16
JournalJournal of Cell Biology
Volume193
Issue number4
DOIs
StatePublished - May 16 2011

ASJC Scopus subject areas

  • Cell Biology

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