title: Dpp/Gbb signaling is required for normal intestinal regeneration during infection.
abstract: Maintaining tissue homeostasis is a critical process during infection and inflammation. Tissues with a high intrinsic turnover, such as the intestinal epithelium, must launch a rapid response to infections while simultaneously coordinating cell proliferation and differentiation decisions. In this study, we searched for genes required for regeneration of the Drosophila intestine, and thereby affecting overall organism survival after infection with pathogenic bacteria. We found that Dpp/Gbb (BMP) signaling is essential for normal midgut regeneration, and that infection induces the BMP signaling ligands Dpp and Gbb. We demonstrate that Dpp is induced in visceral muscle and required for signaling activation. Subsequently, Gbb is induced in enterocytes after oral infection. Loss-of Dpp signaling in ISCs and transient committed progenitors called enteroblasts (EBs), or in EBs alone, led to a blockage in EC differentiation or maturation. Furthermore, our data show that down-regulation of Dpp signaling in the precursor cells including EBs also resulted in an increased number of abnormally small Pdm1-positive cells, suggesting a role of Dpp/Gbb signaling in EC growth. In addition, we show that Dpp/Gbb signaling acted downstream or in parallel to the Notch pathway to promote EC differentiation and growth. Our results suggest that Dpp/BMP signaling plays an important role in EBs to maintain tissue integrity and homeostasis during pathogenic infections.
authors.affiliation: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department for Cell and Molecular Biology, Medical Faculty Mannheim, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: German Cancer Research Center (DKFZ) - Center for Molecular Biology Heidelberg (ZMBH) Alliance, 69120 Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Florescu
authors.affiliation: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department for Cell and Molecular Biology, Medical Faculty Mannheim, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Anna-Lisa
authors.initials: AL
authors.lastname: Boettcher
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, 117604 Singapore; Department of Biological Sciences, National University of Singapore, 117543 Singapore.
authors.forename: Lichao
authors.initials: L
authors.lastname: Luo
authors.affiliation: German Cancer Research Center (DKFZ) - Center for Molecular Biology Heidelberg (ZMBH) Alliance, 69120 Heidelberg, Germany.
authors.forename: Devanjali
authors.initials: D
authors.lastname: Dutta
authors.affiliation: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department for Cell and Molecular Biology, Medical Faculty Mannheim, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
authors.forename: Grainne
authors.initials: G
authors.lastname: Kerr
authors.affiliation: Temasek Life Sciences Laboratory, National University of Singapore, 117604 Singapore; Department of Biological Sciences, National University of Singapore, 117543 Singapore.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: German Cancer Research Center (DKFZ) - Center for Molecular Biology Heidelberg (ZMBH) Alliance, 69120 Heidelberg, Germany.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Edgar
authors.affiliation: German Cancer Research Center (DKFZ), Division Signaling and Functional Genomics and Heidelberg University, Department for Cell and Molecular Biology, Medical Faculty Mannheim, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. Electronic address: m.boutros@dkfz.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Boutros
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D004330:Drosophila / Q000382:microbiology / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D015723:Gene Library; D059014:High-Throughput Nucleotide Sequencing; D007413:Intestinal Mucosa / Q000382:microbiology / Q000502:physiology*; D018613:Microscopy, Confocal; D009132:Muscles / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; C089440:gbb protein, Drosophila
keywords: Dpp/Gbb signaling; Drosophila; EC differentiation; Infection; Stem cells