Summary
In adult organisms, gut barrier function is maintained by adapting the proliferation and turnover of resident intestinal stem cells (ISCs) to environmental cues. In recent years, an immense effort in the field has successfully identified many short and long-range signals involved in ISC-driven adaptive growth responses. However, it is becoming increasingly evident that biomechanical cues, such as shear stress, compressions, swellings, and tissue-scale tension, also play a key role in regulating SC activity in adult tissues. Hence, the adult gut is constantly exposed to mechanical stress and must adapt accordingly to the stretch and strain. Despite the undisputed impact that mechanical forces have on adult organ physiology, very little is known about the molecular signals involved. Using Drosophila as a model, we performed a genetic screen for ISC niche receptors coupling environmental cues with ISC-dependent adaptive growth and identified several receptors belonging to mechanotransduction pathways as indispensable for preserving gut barrier function. Mechanical forces can be either of tissue intrinsic origin, such as forces emanating from cell division and cell death, or of external origins, such as those originating from extracellular matrix remodeling, mechanical coupling to neighboring tissues, and food and fluid flow. Recent studies in developing embryos and during tissue morphogenesis show that cells can sense mechanical forces through mechanotransducer proteins, and are used as cues to regulate gene expression patterns, cell fate specifications, cell packing, and proliferation. An insight into mechanosensation in regulating ISC niche homeostasis in mature organs is still lacking and given my scientific background in biophysics and mechanobiology, this study aims to understand the role of mechanosensory inputs in maintaining the ISC niche using the Drosophila adult gut as a model system.
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| Web resources: | https://cordis.europa.eu/project/id/101109581 |
| Start date: | 01-02-2024 |
| End date: | 31-01-2026 |
| Total budget - Public funding: | - 230 774,00 Euro |
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Original description
In adult organisms, gut barrier function is maintained by adapting the proliferation and turnover of resident intestinal stem cells (ISCs) to environmental cues. In recent years, an immense effort in the field has successfully identified many short and long-range signals involved in ISC-driven adaptive growth responses. However, it is becoming increasingly evident that biomechanical cues, such as shear stress, compressions, swellings, and tissue-scale tension, also play a key role in regulating SC activity in adult tissues. Hence, the adult gut is constantly exposed to mechanical stress and must adapt accordingly to the stretch and strain. Despite the undisputed impact that mechanical forces have on adult organ physiology, very little is known about the molecular signals involved. Using Drosophila as a model, we performed a genetic screen for ISC niche receptors coupling environmental cues with ISC-dependent adaptive growth and identified several receptors belonging to mechanotransduction pathways as indispensable for preserving gut barrier function. Mechanical forces can be either of tissue intrinsic origin, such as forces emanating from cell division and cell death, or of external origins, such as those originating from extracellular matrix remodeling, mechanical coupling to neighboring tissues, and food and fluid flow. Recent studies in developing embryos and during tissue morphogenesis show that cells can sense mechanical forces through mechanotransducer proteins, and are used as cues to regulate gene expression patterns, cell fate specifications, cell packing, and proliferation. An insight into mechanosensation in regulating ISC niche homeostasis in mature organs is still lacking and given my scientific background in biophysics and mechanobiology, this study aims to understand the role of mechanosensory inputs in maintaining the ISC niche using the Drosophila adult gut as a model system.Status
SIGNEDCall topic
HORIZON-MSCA-2022-PF-01-01Update Date
31-07-2023
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