CoordinGrowthDev · Characterization of the mechanism of inter-organ communication coordinating tissue growth and developmental timing

Characterization of the mechanism of inter-organ communication coordinating tissue growth and developmental timing

Over the recent years, research in developmental biology has stumbled upon the problem of how development ensures that organisms achieve appropriate body and organ size. The coordination of organ growth with the developmental program is essential for the emergence of adults with proper body size and proportions. These species-specific features condition many traits of adult life such as fitness and survival. Studies on fruit flies have allowed setting up the conceptual frame for this critical research. Our current understanding is that tissue growth and the developmental program are synchronized by feedback control mechanisms that block the transition to the next developmental period until all tissues have completed growth. Yet, we still lack a coherent picture of how these feedbacks operate at the organism level from a mechanistic point of view. Recent work in Drosophila has started unraveling the nature of the signals that couple tissue growth with developmental progression. The relaxin-like peptide Dilp8 is key in this coupling, raising the possibility that peptides with similar roles may exist in vertebrates. Dilp8 is secreted by growing, regenerating and tumorous tissues. It acts remotely on steroid hormone production to inhibit the transition to the pupal stage and to delay development. In addition, the negative impact of Dilp8 on tissue growth suggests that it could act as a synchronization factor among growing tissues. The current project aimed at characterizing the molecular mechanisms by which Dilp8 coordinates development of the different body parts. To do so, we have identified and characterized the receptor for Dilp8, the relaxin family receptor Lgr3. In addition, we functionally identified two Lgr3-positive neurons in each brain lobe that are required for Dilp8 functions. Reducing Lgr3 levels in these neurons results in adult flies exhibiting increased fluctuating bilateral symmetry, therefore recapitulating the phenotype of dilp8 mutants. Our work revealed a novel Dilp8/Lgr3 neuronal circuitry involved in a feedback mechanism that ensures coordination between organ growth and developmental transitions and prevents developmental variability. Finally, ongoing work focuses on the role of Dilp8 in inter-organ coordination of tissue growth, with an emphasis on the molecular mechanism linking organ growth status with Dilp8 upregulation and the systemic response.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз