title: EGFR/MAPK signaling regulates the proliferation of Drosophila renal and nephric stem cells.
abstract: Tissue homeostasis, accomplished through the self-renewal and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal's lifetime. Adult Drosophila Malpighian tubules (MTs or fly kidney) are maintained by renal and nephric stem cells (RNSCs) via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inactivation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts (RBs), the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.
authors.affiliation: College of Life Sciences, Capital Normal University, Beijing 100048, China; Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore. Electronic address: zhli@cnu.edu.cn.
authors.forename: Zhouhua
authors.initials: Z
authors.lastname: Li
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore.
authors.forename: Sen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, Singapore 117604, Singapore; Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore. Electronic address: caiyu@tll.org.sg.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D018010:Receptors, Invertebrate Peptide / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C102284:Myc protein, Drosophila; D018010:Receptors, Invertebrate Peptide; D014157:Transcription Factors; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Drosophila Malpighian tubules; EGFR/MAPK signaling; Renal and nephric stem cells