Smith, Hannah J., Lanjuin, Anne, Towbin, Benjamin D., Mair, William B., Stojanovski, Klement, Gheorghe, Ioana
[
International Worm Meeting,
2021]
Reaching appropriate organ size proportions is crucial for organismal function. However, size proportions are intrinsically challenged by stochastic fluctuations in the growth rate of organs. Although, in principle, small heterogeneities in the growth rate can amplify to large differences in their size during development, organ size proportions are remarkably uniform among isogenic individuals. We therefore hypothesised that organs coordinate their growth and size with each other. To test this hypothesis and understand the mechanism involved, we used the AID/TIR1 to systematically inhibit mTOR signalling in individual tissues. The mTOR pathway is a conserved and central regulator of cellular growth that is thought to act cell autonomously. However, we find that tissue-specific inhibition of mTOR also has large systemic effects on other tissues. For example, pharynx-specific depletion of mTOR is associated with a global reduction of body growth. Depletion of mTOR in the pharynx led to a 2-fold reduction in the adult body size, but did not cause a deviation from the appropriate pharynx-to-body size proportions. To unravel the inter-cellular signalling network that coordinates organ growth, we are currently conducting a genome-wide high content RNAi screen for supressors and enhancers of this phenotype.
Lanjuin, Anne, Towbin, Benjamin D., Stojanovski, Klement, Mair, William B., Gheorghe, Ioana, Smith, Hannah J.
[
International Worm Meeting,
2021]
Organs need to grow to their appropriate size during development, and even small deviations from the correct size can impair organismal function. For example, discrepancies of only a few percent between the length of our legs severely impair motility. Although, in principle, small differences in the growth rate of different organs could amplify to large differences in their size, deviations from the appropriate organ size proportions are rarely observed in nature. However, the mechanisms involved in maintenance of organ size homeostasis are poorly understood. We use live imaging of gastrointestinal growth of C. elegans to study the mechanism of organ size uniformity among individuals. We followed hundreds of individuals from birth to adulthood and measured pharyngeal and total body growth at a temporal resolution of 10 minutes. Individuals differed substantially in their pharyngeal growth rates. Nevertheless, the heterogeneity in pharyngeal size did not increase during development, suggesting a mechanism that senses and counteracts deviations from the appropriate organ size proportions. Indeed, pharynx-specific inhibition of mTOR slowed down pharyngeal growth but did not alter pharyngeal size proportions, as the slow-down of pharyngeal growth was accompanied by an appropriate growth reduction of other tissues. In conclusion, we provide strong evidence for the systemic coordination of tissue growth of C. elegans. The present experimental system provides an exciting opportunity to identify the molecules involved in this coordination by genetic screens.