Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Developmental control of animal size: mechanisms and evolution

In plain English

AI plain-English summary

A fruit fly’s abdomen stops growing at precisely the right size, and this project will find out how. Organs in animals—including humans—grow to a characteristic size and then stop. When that control fails, the result can be cancer. Yet scientists do not have a clear model of how growth shuts down on cue. The same puzzle applies across evolution: different species of fruit fly have different-sized abdomens, but the cellular and molecular reasons for those differences are largely unknown. This project will use the fruit fly *Drosophila melanogaster* as a model, combining live imaging, genetic tools, and quantitative biology to identify the signals that terminate growth at the correct time. It will then compare growth mechanisms across several *Drosophila* species to understand how organ size evolves. This is fundamental science. It will not produce a drug or a device. But understanding how growth is normally controlled is essential for grasping what goes wrong in cancer, and for designing regenerative therapies that restore tissue without overgrowth. Past discoveries in *Drosophila* have revealed core principles of development and disease that apply directly to humans. This work could lay the groundwork for future applications in oncology and regenerative medicine.

View original technical description
How do organs reach their appropriate size during animal development? Unravelling organ size control is key to understanding growth pathologies such as cancer and fulfilling the potential of regenerative medicine. Although we know many signals that can modulate developmental growth, we lack a coherent model of how growth ceases at the correct time. Furthermore, although differences in body size and proportions across species are among the most striking aspects of animal evolution, the cellular and molecular bases for these differences remain little explored. Here, we exploit the unique live- imaging and genetic tractability of the fruit fly Drosophila melanogaster abdominal epidermis to ask how growth is terminated at the appropriate size in a developing system. We will combine rigorous quantitative biology with temporal genomics and a candidate approach to identify the signals that ensure the robust control of tissue size during development (Aim 1). We will take advantage of the broad variation in abdomen sizes across the Drosophila genus and the precision of our quantitative approach to developmental growth in the abdominal epidermis to explore tissue size control in differently sized Drosophila species. We will ask what cellular behaviours and molecular mechanisms underpin the evolution of organ size (Aim 2).

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Researchers

Nicolas Tapon (EPMC Awardee)

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Original classification

Discovery Award

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