GrowthControl · Mechanical and systemic control of growth during Drosophila abdominal development
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2018-03-01 → 2020-02-29
- EU contribution
- €183,455
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
Lines connect the coordinator with its partners.
Results in brief
Mechanical and systemic control of growth during Drosophila abdominal development
Many signalling pathways have been shown to influence final tissue size. However, whether and how their activities change to signal growth arrest in a timely fashion during development remains unclear. Therefore, the knowledge about the mechanisms that regulate how cell proliferation is triggered in response to different extrinsic as well as intrinsic stimuli and how transitions between different proliferative states are controlled is very limited. Not only it is important to understand how proliferation is controlled during development, but it is particularly essential to unravel how proliferation is driven in tumour cells or regenerative tissues. We wanted to understand how mechanical forces and systemic cues contribute to the different growth and proliferative phases a tissue undergoes throughout its development, as well as to final tissue growth arrest, using the abdominal epithelium of Drosophila melanogaster as a model system. Likewise, we aimed to investigate how systemic growth signalling pathways are integrated with the physical properties of a tissue. We have explored how nutrient-sensing signalling pathways influence growth and proliferation as well as whether underlying changes in the mechanical properties of a tissue can account for changes in the proliferative state. This work showed that although nutrient-sensing pathways impact on cell growth during specific developmental phases, they do not appear to dictate proliferation arrest. Unlike what has been proposed in other organs, tissue mechanics does not seem to impact the proliferation state of cells in the abdominal epithelium. We believe that the work developed here has furthered our fundamental understanding of developmental growth regulation, and as such drive further investigation in cancer biology, disease models and regeneration studies.
Data: CORDIS, © European Union
Project objective
Control of tissue size during animal development is of crucial importance to achieve the correct body/organ size and shape, and it underpins the evolution of animal size and architecture. How is tissue size tightly controlled during development? How is each cell in a developing animal instructed to stop growing and dividing when the correct body size and shape has been reached? Answers to these questions are of fundamental importance to our understanding of diseases such as cancer as well as for regenerative medicine. Using the development of the Drosophila abdominal epidermis as a model, we will perform long-term quantitative in vivo analysis of cellular behaviours and generate fluorescent live reporters of growth-promoting pathways to correlate activity patterns with developmentally regulated growth phases. We will manipulate tissue mechanics as well as nutrient-sensing pathways to understand how nutrient availability and tissue-intrinsic physical properties are integrated to specify final tissue size. In combination with computational modelling, we aim to generate a better understanding of developmental growth, as well as the mechanisms that trigger tissue growth arrest. The mechanisms regulating how cell proliferation is triggered in response to extrinsic and intrinsic stimuli and the transitions between different proliferative/growth states, particularly in tumour cells or regenerative tissues, are poorly understood. As these events are precisely defined in Drosophila abdominal morphogenesis, we hope to uncover the internal logic modulating cell cycle/growth rates transitions that can be used as a genetically tractable paradigm for the study of equivalent processes in cancer, regeneration or development.
Original text from CORDIS.
Participants
- THE FRANCIS CRICK INSTITUTE LIMITED · LondonCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union