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Updated: Mar 20, 2026
Live Imaging Of Drosophila melanogaster Embryonic Hemocyte Migrations
Published on: February 12, 2010
Remote Control of Intestinal Stem Cell Activity by Haemocytes in Drosophila
Sveta Chakrabarti1, Jan Paul Dudzic1, Xiaoxue Li1
1Global Health Institute, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Insights
Injury triggers the release of Upd3 from Drosophila immune cells, activating the JAK/STAT pathway. This remotely stimulates gut stem cell repair, crucial for survival after septic injury.
Area of Science:
- Cellular and Molecular Biology
- Immunology
- Developmental Biology
Background:
- The Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway regulates development and immunity.
- In Drosophila, a single canonical JAK/STAT pathway is activated by Unpaired (Upd) proteins.
- The precise role of this pathway in the systemic immune response to tissue damage is not fully understood.
Purpose of the Study:
- To investigate the role of the JAK/STAT pathway in the Drosophila systemic immune response using upd2 and upd3 mutations.
- To elucidate the activation mechanism and specific functions of JAK/STAT signaling in response to injury.
Main Methods:
- Utilized mutations in upd2 and upd3 to study the JAK/STAT pathway.
- Investigated gene expression of upd genes in haemocytes.
- Examined the effects of Upd3 release on stem cell proliferation and gene expression in the intestine.
- Assessed survival rates following septic injury and oral bacterial infection.
Main Results:
- Haemocytes express all three upd genes; injury induces upd3 expression via the JNK pathway.
- Upd3 released from haemocytes activates the JAK/STAT pathway in the fat body and gut, stimulating stem cell proliferation and Drosomycin-like gene expression.
- Intestinal stem cell renewal is essential for survival after septic injury.
- Haemocytes promote gut stem cell activation and survival during septic injury but are not required for gut renewal after oral bacterial infection.
Conclusions:
- Haemocyte-derived Upds coordinate a wound-healing response across multiple tissues, including the gut.
- Intestinal epithelium renewal is sensitive to both luminal and haemocoel insults.
- Maintaining gut integrity is critical for fly survival following systemic injury.
Abstract:
The JAK/STAT pathway is a key signaling pathway in the regulation of development and immunity in metazoans. In contrast to the multiple combinatorial JAK/STAT pathways in mammals, only one canonical JAK/STAT pathway exists in Drosophila. It is activated by three secreted proteins of the Unpaired family (Upd): Upd1, Upd2 and Upd3. Although many studies have established a link between JAK/STAT activation and tissue damage, the mode of activation and the precise function of this pathway in the Drosophila systemic immune response remain unclear. In this study, we used mutations in upd2 and upd3 to investigate the role of the JAK/STAT pathway in the systemic immune response. Our study shows that haemocytes express the three upd genes and that injury markedly induces the expression of upd3 by the JNK pathway in haemocytes, which in turn activates the JAK/STAT pathway in the fat body and the gut. Surprisingly, release of Upd3 from haemocytes upon injury can remotely stimulate stem cell proliferation and the expression of Drosomycin-like genes in the intestine. Our results also suggest that a certain level of intestinal epithelium renewal is required for optimal survival to septic injury. While haemocyte-derived Upd promotes intestinal stem cell activation and survival upon septic injury, haemocytes are dispensable for epithelium renewal upon oral bacterial infection. Our study also indicates that intestinal epithelium renewal is sensitive to insults from both the lumen and the haemocoel. It also reveals that release of Upds by haemocytes coordinates the wound-healing program in multiple tissues, including the gut, an organ whose integrity is critical to fly survival.
