title: Tuberous sclerosis complex and Myc coordinate the growth and division of Drosophila intestinal stem cells.
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.
authors.affiliation: University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Alla
authors.initials: A
authors.lastname: Amcheslavsky
authors.forename: Naoto
authors.initials: N
authors.lastname: Ito
authors.forename: Jin
authors.initials: J
authors.lastname: Jiang
authors.forename: Y Tony
authors.initials: YT
authors.lastname: Ip
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D049108:Cell Enlargement / Q000187:drug effects; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D009154:Mutation; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102284:Myc protein, Drosophila; D047428:Protein Kinase Inhibitors; C515347:TSC1 protein, Drosophila; D014157:Transcription Factors; C117726:gig protein, Drosophila; D011494:Protein Kinases; C416303:target of rapamycin protein, Drosophila; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus