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Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration
Phillip Karpowicz1, Jessica Perez, Norbert Perrimon
1Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. pkarpowicz@genetics.med.harvard.edu
Development (Cambridge, England)
|November 25, 2010
Summary
The Hippo pathway’s Yorkie (Yki) protein acts within intestinal stem cells (ISCs) to control their proliferation. This cell-autonomous function is repressed by Fat and Dachsous (Ds) before injury, impacting tissue repair and cancer.
Area of Science:
- Cell biology
- Developmental biology
- Stem cell biology
Background:
- Stem cell (SC) proliferation is crucial for tissue homeostasis and cancer.
- In Drosophila midgut, JNK and JAK/STAT pathways regulate SC proliferation after injury.
- The Hippo pathway is implicated in regulating cytokine production.
Purpose of the Study:
- To investigate the cell-autonomous role of the Hippo pathway in intestinal stem cells (ISCs).
- To identify the specific functions and regulators of the Hippo pathway within ISCs.
Main Methods:
- Genetic manipulation of Hippo pathway components in Drosophila midgut.
- Analysis of stem cell proliferation and gene expression.
- Investigation of upstream regulators of Yorkie (Yki) activity.
Main Results:
- Hippo pathway target Yorkie (Yki) acts cell-autonomously in ISCs to promote proliferation.
- Yki activation in ISCs increases division, survival, and Upd cytokine production.
- Upstream Hippo pathway members Fat and Dachsous (Ds) repress Yki activity in ISCs prior to injury.
Conclusions:
- The Hippo pathway plays a cell-autonomous role in regulating intestinal stem cell proliferation.
- Findings provide insights into stem cell regulation, tissue repair, and cancer stem cell biology.
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