A Phyllopod-Mediated Feedback Loop Promotes Intestinal Stem Cell Enteroendocrine Commitment in Drosophila
1Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China; National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China.
Stem Cell Reports
|December 26, 2017
Summary
Researchers discovered Phyllopod (Phyl) regulates enteroendocrine cell (EE) generation from Drosophila intestinal stem cells (ISCs). A positive feedback loop involving Phyl, Tramtrack 69 (Ttk69), and the Achaete-Scute Complex (AS-C) ensures EE cell fate commitment.
Area of Science:
- Developmental Biology
- Stem Cell Biology
- Drosophila melanogaster research
Background:
- The Drosophila midgut epithelium relies on intestinal stem cells (ISCs) for renewal and differentiation.
- ISCs generate enterocytes and enteroendocrine cells (EEs) through distinct cell fate pathways.
- Delta-Notch signaling is known to promote enterocyte generation, but EE generation mechanisms are unclear.
Purpose of the Study:
- To elucidate the molecular mechanisms governing enteroendocrine cell (EE) generation from Drosophila intestinal stem cells (ISCs).
- To identify key regulators involved in the alternative cell fate specification of ISCs towards EE lineage.
- To understand the regulatory network controlling EE fate commitment.
Main Methods:
- Utilized Drosophila midgut as a model system for studying intestinal stem cell differentiation.
- Investigated the role of Phyllopod (Phyl) in EE cell fate specification.
- Analyzed protein-protein interactions and regulatory pathways involving Phyl, Tramtrack 69 (Ttk69), Sina, and the Achaete-Scute Complex (AS-C).
Main Results:
- Identified Phyllopod (Phyl) as a crucial regulator promoting EE generation from ISCs.
- Demonstrated that Phyl facilitates the degradation of Tramtrack 69 (Ttk69) via interaction with Sina.
- Showed that Ttk69 degradation activates the Achaete-Scute Complex (AS-C)-Pros regulatory axis, driving EE specification.
- Discovered a positive feedback loop where AS-C gene expression induces further Phyl expression, reinforcing EE commitment.
Conclusions:
- Phyllopod (Phyl) is a key adaptor protein essential for enteroendocrine cell (EE) fate determination in Drosophila.
- A novel regulatory cascade involving Phyl, Ttk69, Sina, and AS-C controls EE specification from intestinal stem cells (ISCs).
- The identified positive feedback mechanism ensures reliable and irreversible EE cell fate commitment, potentially a conserved strategy in progenitor cell differentiation.
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