title: During Drosophila disc regeneration, JAK/STAT coordinates cell proliferation with Dilp8-mediated developmental delay.
abstract: Regeneration of fragmented Drosophila imaginal discs occurs in an epimorphic manner involving local cell proliferation at the wound site. After disc fragmentation, cells at the wound site activate a restoration program through wound healing, regenerative cell proliferation, and repatterning of the tissue. However, the interplay of signaling cascades driving these early reprogramming steps is not well-understood. Here, we profiled the transcriptome of regenerating cells in the early phase within 24 h after wounding. We found that JAK/STAT signaling becomes activated at the wound site and promotes regenerative cell proliferation in cooperation with Wingless (Wg) signaling. In addition, we showed that the expression of Drosophila insulin-like peptide 8 (dilp8), which encodes a paracrine peptide to delay the onset of pupariation, is controlled by JAK/STAT signaling in early regenerating discs. Our findings suggest that JAK/STAT signaling plays a pivotal role in coordinating regenerative disc growth with organismal developmental timing.
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, 4058 Basel, Switzerland;
authors.forename: Tomonori
authors.initials: T
authors.lastname: Katsuyama
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, 4058 Basel, Switzerland;
authors.forename: Federico
authors.initials: F
authors.lastname: Comoglio
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, 4058 Basel, Switzerland;
authors.forename: Makiko
authors.initials: M
authors.lastname: Seimiya
authors.affiliation: Single Cell Genomics, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; and.
authors.forename: Erik
authors.initials: E
authors.lastname: Cabuy
authors.affiliation: Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zürich, 4058 Basel, Switzerland; Faculty of Science, University of Basel, 4056 Basel, Switzerland renato.paro@bsse.ethz.ch.
authors.forename: Renato
authors.initials: R
authors.lastname: Paro
mesh_terms: D000818:Animals; D019521:Body Patterning; D019070:Cell Lineage; D049109:Cell Proliferation; D016000:Cluster Analysis; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D060227:Imaginal Discs / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D053612:Janus Kinases / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012038:Regeneration; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D014945:Wound Healing
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D050791:STAT Transcription Factors; D014157:Transcription Factors; C572149:insulin-like peptide 8, Drosophila; D053612:Janus Kinases; C085845:hop protein, Drosophila
keywords: Drosophila imaginal discs; JAK/STAT signaling; epimorphic regeneration