Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2013-09-01Keywords
AnimalsBleomycin
Cell Differentiation
Cell Proliferation
DNA-Binding Proteins
Dextran Sulfate
Drosophila
Drosophila Proteins
Female
Green Fluorescent Proteins
Intestines
Intracellular Signaling Peptides and Proteins
Janus Kinases
Nuclear Proteins
Protein-Serine-Threonine Kinases
RNA Interference
RNA, Small Interfering
Receptor, Epidermal Growth Factor
Receptors, Invertebrate Peptide
STAT Transcription Factors
Signal Transduction
Stem Cells
Trans-Activators
Transcription Factors
Transcription, Genetic
Cell Biology
Cells
Cellular and Molecular Physiology
Digestive System
Metadata
Show full item recordAbstract
Intestinal stem cells (ISCs) in the Drosophila adult midgut are essential for maintaining tissue homeostasis, and their proliferation and differentiation speed up in order to meet the demand for replenishing the lost cells in response to injury. Several signaling pathways including JAK-STAT, EGFR and Hippo (Hpo) pathways have been implicated in damage-induced ISC proliferation, but the mechanisms that integrate these pathways have remained elusive. Here, we demonstrate that the Drosophila homolog of the oncoprotein Myc (dMyc) functions downstream of these signaling pathways to mediate their effects on ISC proliferation. dMyc expression in precursor cells is stimulated in response to tissue damage, and dMyc is essential for accelerated ISC proliferation and midgut regeneration. We show that tissue damage caused by dextran sulfate sodium feeding stimulates dMyc expression via the Hpo pathway, whereas bleomycin feeding activates dMyc through the JAK-STAT and EGFR pathways. We provide evidence that dMyc expression is transcriptionally upregulated by multiple signaling pathways, which is required for optimal ISC proliferation in response to tissue damage. We have also obtained evidence that tissue damage can upregulate dMyc expression post-transcriptionally. Finally, we show that a basal level of dMyc expression is required for ISC maintenance, proliferation and lineage differentiation during normal tissue homeostasis.Source
Cell Res. 2013 Sep;23(9):1133-46. doi: 10.1038/cr.2013.101. Epub 2013 Jul 30. Link to article on publisher's siteDOI
10.1038/cr.2013.101Permanent Link to this Item
http://hdl.handle.net/20.500.14038/30331PubMed ID
23896988Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/cr.2013.101
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