Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration

Fangfang Ren, Qing Shi, Yongbin Chen, Alice Jiang, Y. Tony Ip, Huaqi Jiang, Jin Jiang

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1133-1146
Number of pages14
JournalCell Research
Volume23
Issue number9
DOIs
StatePublished - Sep 2013

Fingerprint

Drosophila
Regeneration
Stem Cells
Cell Proliferation
Homeostasis
Dextran Sulfate
Oncogene Proteins
Bleomycin
Cell Lineage
Up-Regulation
Maintenance
Wounds and Injuries

Keywords

  • EGFR
  • Hpo
  • ISC
  • JAK-STAT
  • Myc
  • regeneration

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration. / Ren, Fangfang; Shi, Qing; Chen, Yongbin; Jiang, Alice; Ip, Y. Tony; Jiang, Huaqi; Jiang, Jin.

In: Cell Research, Vol. 23, No. 9, 09.2013, p. 1133-1146.

Research output: Contribution to journalArticle

Ren, Fangfang ; Shi, Qing ; Chen, Yongbin ; Jiang, Alice ; Ip, Y. Tony ; Jiang, Huaqi ; Jiang, Jin. / Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration. In: Cell Research. 2013 ; Vol. 23, No. 9. pp. 1133-1146.
@article{675c90ea95324ce29c2a9bfc28b4e2c7,
title = "Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration",
abstract = "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.",
keywords = "EGFR, Hpo, ISC, JAK-STAT, Myc, regeneration",
author = "Fangfang Ren and Qing Shi and Yongbin Chen and Alice Jiang and Ip, {Y. Tony} and Huaqi Jiang and Jin Jiang",
year = "2013",
month = "9",
doi = "10.1038/cr.2013.101",
language = "English (US)",
volume = "23",
pages = "1133--1146",
journal = "Cell Research",
issn = "1001-0602",
publisher = "Nature Publishing Group",
number = "9",

}

TY - JOUR

T1 - Drosophila Myc integrates multiple signaling pathways to regulate intestinal stem cell proliferation during midgut regeneration

AU - Ren, Fangfang

AU - Shi, Qing

AU - Chen, Yongbin

AU - Jiang, Alice

AU - Ip, Y. Tony

AU - Jiang, Huaqi

AU - Jiang, Jin

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

KW - EGFR

KW - Hpo

KW - ISC

KW - JAK-STAT

KW - Myc

KW - regeneration

UR - http://www.scopus.com/inward/record.url?scp=84883455449&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883455449&partnerID=8YFLogxK

U2 - 10.1038/cr.2013.101

DO - 10.1038/cr.2013.101

M3 - Article

VL - 23

SP - 1133

EP - 1146

JO - Cell Research

JF - Cell Research

SN - 1001-0602

IS - 9

ER -