H2020Individual fellowship2020–2022

GrowthDevStability · Characterization of the developmental mechanisms ensuring a robust symmetrical growth in the bilateral model organism Drosophila melanogaster

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-06-01 → 2022-05-31
EU contribution
€184,708
Participants
1
Scheme
MSCA-IF-EF-ST

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Results in brief

Characterization of the developmental mechanisms ensuring a robust symmetrical growth in the bilateral model organism Drosophila melanogaster

Most animals, including humans, have one longitudinal or sagittal plane which divides the organism into two roughly mirror images, the left and right halves. For example, the surfaces of the two wings of the fruit fly Drosophila melanogaster, a privileged model organism, do not differ by more than 2% in wild-type animals. This feature is called Bilateral Symmetry and constitutes a key quality that defines mobility, predation and overall fitness. Even though many studies have focused on the autonomous mechanisms of organ size determination, less attention has been put on how organ growth is coordinated between the left and right halves in order to attain Bilateral Symmetry. The fact that symmetry is achieved even in the case of illness, starvation and injuries, suggests the occurrence of dedicated mechanisms that are able to compare the growth trajectories of each half and adjust when required. The investigation on how Bilateral Symmetry is achieved has profound impacts, not only because it constitutes a fundamental question in Developmental Biology but also because it is directly linked to animal and human health and technology. The new concepts introduced by this investigation could help to better understand the pathophysiology of childhood growth disorders, as well as the growth disturbances observed in cancer survivors. It would also certainly have implications for large-scale regenerative research, in which a tight coordination of left and right halves should be attained. The overarching objective of the proposed project was to find how and when organs asses their growth status in Drosophila, and which mechanisms are deployed to ensure fine size adjustment during normal animal development. In particular, my research was focused of the role of a signaling peptide that belongs to the superfamily of insulin/IGF/relaxin-like peptidic hormones and is called Drosophila insulin-like peptide 8 (Dilp8). I sought to characterize the source tissue that produces dilp8, how and when this production is induced, and what are the downstream events that dilp8 triggers for bilateral organ size adjustment. After my two years of MSCA-funded research, the research team and I were able to define a cross-talk between Dilp8 and the growth-regulating hormone ecdysone that is key for developmental precision. This cross-talk has two functions: (i) it defines a critical time window after larval development during which wings adjust their size; (ii) it fine-tunes the levels of ecdysone signaling in the discs, which is crucial for their size adjustment.

Data: CORDIS, © European Union

Project objective

The overarching objective of the proposed project is to find how and when organs asses their growth status and which mechanisms are deployed to ensure fine size adjustment during normal animal development. As a model system, I will study the symmetrical growth of D. melanogaster, where the signaling hormone Dilp8 has been described as a central player to ensure developmental stability. However, Dilp8 regulation and mechanism of action remain elusive, providing an unprecedented framework to inquiry about the general phenomenon of growth adjustment. I will study when Dilp8 is required and in which organ it is produced during normal development. Also, I will identify signaling pathways regulating Dilp8 expression and the downstream effectors required for its action. This project will allow me to define for the first time how a systemic signal is activated and functions to adjust symmetrical growth in a bilateral model organism. The new concepts introduced by my investigation may help to better understand the pathophysiology of childhood growth disorders, as well as the growth disturbances observed in cancer survivors.

Original text from CORDIS.

Participants

  • INSTITUT CURIE · ParisCoordinatorFrance

Links

Data: CORDIS, © European Union