Related Experiment Video
Updated: Dec 28, 2025
Induction and Diagnosis of Tumors in Drosophila Imaginal Disc Epithelia
Published on: July 25, 2017
A Switch in Tissue Stem Cell Identity Causes Neuroendocrine Tumors in Drosophila Gut
Zhaohui Li1, Xingting Guo2, Huanwei Huang2
1National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
Abstract:
Intestinal stem cells (ISCs) are able to generate gut-specific enterocytes, as well as neural-like enteroendocrine cells. It is unclear how the tissue identity of the ISC lineage is regulated to confer cell-lineage fidelity. Here, we show that, in adult Drosophila midgut, loss of the transcriptional repressor Tramtrack in ISCs causes a self-renewal program switch to neural stem cell (NSC)-like, and that switch drives neuroendocrine tumor development. In Tramtrack-depleted ISCs, the ectopically expressed Deadpan acts as a major self-renewal factor for cell propagation, and Sequoia acts as a differentiation factor for the neuroendocrine phenotype. In addition, the expression of Sequoia renders NSC-specific self-renewal genes responsive to Notch in ISCs, thus inverting the differentiation-promoting function of Notch into a self-renewal role as in normal NSCs. These results suggest an active maintenance mechanism for the gut identity of ISCs, whose disruption may lead to an improper acquisition of NSC-like traits and tumorigenesis.
Insights
Disrupting the transcriptional repressor Tramtrack in intestinal stem cells (ISCs) causes them to adopt neural stem cell (NSC)-like traits, driving neuroendocrine tumor development in Drosophila midgut. This highlights an active mechanism maintaining gut identity.
Area of Science:
- Developmental biology
- Stem cell biology
- Cancer biology
Background:
- Intestinal stem cells (ISCs) maintain gut tissue homeostasis by generating specific cell types.
- The mechanisms regulating ISC tissue identity and preventing lineage infidelity remain largely unknown.
- Disruption of ISC identity can lead to tumorigenesis, particularly neuroendocrine tumors.
Purpose of the Study:
- To investigate the role of the transcriptional repressor Tramtrack in maintaining Drosophila intestinal stem cell identity.
- To elucidate the molecular mechanisms underlying the switch from ISC to neural stem cell (NSC)-like states.
- To understand how this switch contributes to neuroendocrine tumor development.
Main Methods:
- Utilized Drosophila adult midgut as a model system.
- Employing genetic manipulation to deplete the transcriptional repressor Tramtrack in ISCs.
- Analyzing the expression and function of key transcription factors like Deadpan and Sequoia.
- Investigating the role of the Notch signaling pathway in ISC self-renewal and differentiation.
Main Results:
- Loss of Tramtrack in ISCs triggers a switch to an NSC-like self-renewal program.
- Ectopic expression of Deadpan promotes ISC proliferation, while Sequoia drives neuroendocrine differentiation.
- Sequoia expression alters NSC-specific gene regulation by Notch, inverting its typical differentiation role to one of self-renewal.
- Disruption of ISC identity leads to neuroendocrine tumor formation.
Conclusions:
- The gut identity of ISCs is actively maintained by specific molecular mechanisms.
- Loss of Tramtrack disrupts this maintenance, leading to acquisition of NSC-like traits.
- This process involves the interplay of Deadpan, Sequoia, and Notch signaling, ultimately resulting in tumorigenesis.
More Related Videos
10:10Sonication-facilitated Immunofluorescence Staining of Late-stage Embryonic and Larval Drosophila Tissues In Situ
Published on: August 14, 2014
07:23A Protocol for Genetic Induction and Visualization of Benign and Invasive Tumors in Cephalic Complexes of Drosophila melanogaster
Published on: September 11, 2013
