Periodic Reporting for period 1 - GrowthControl (Mechanical and systemic control of growth during Drosophila abdominal development)
Periodo di rendicontazione: 2018-03-01 al 2020-02-29
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.
Monitoring signalling activity of Insulin and TOR pathway revealed no specific spatial or temporal pattern throughout histoblasts development. We were not able to uncover any correlation with proliferation and growth parameters, or a change that coincided with the time of proliferation arrest.
We investigated the role of nutrient-sensing pathways in the different growth phases of the abdominal epithelium. While inhibition of Insulin signalling did not have an effect on abdomen development, TOR inhibition caused a delay in histoblasts expansion, as well as a reduced number of cells. Our analysis shows that TOR signalling is only required for histoblasts cell growth during the larval stage, while it is dispensable for expansion of this tissue during the its main period of pupal growth.
By changing the histoblasts’ mechanical environment we demonstrated that, unlike what has been suggested in other tissues, physical forces do not play a role in controlling proliferation rates in the abdominal epithelium.
We also developed a simple numerical model of histoblasts growth that can recapitulate the essential features we observed in the experimental data.
The results generated during our work were presented in several seminars both at the host institute as well as at international conferences. Some results obtained through implementation of this action will be included in a manuscript we have currently in preparation, and we intend to prepare another scientific publication in the next year.
We have shown that nutrient-sensing signalling activity does not show major changes during transitions between different proliferative states and that these signalling pathways do not regulate proliferation arrest in the abdominal epithelium. Although we discovered that there are changes in the tissue stress patterns during development, challenging the mechanical environment was not enough to impact proliferation rates. This is an important point since it was previously suggested, from studies in other tissues, that changes in tissue patterns could account for size control. We aim to further understand how proliferation arrest is regulated in this tissue. We will be exploring this further in the near future.
We believe we made important progress towards an understanding of tissue growth control during the development of an epithelial tissue. We believe the results here uncovered will be of major importance to the growth control and regeneration fields in general. We also hope these methodologies and results can be used for further investigation in other model organisms as well as in cancer biology and other disease models.