Abstract

In the real world, humans and other animals often develop in environments that are suboptimal for metabolism and growth. In these stressful contexts, the growth of key developing organs is prioritized at the expense of others, a process known as organ sparing. It has been clear for many decades that one of the most highly spared organs is the brain, and work in our lab has sought to identify the cellular and molecular mechanisms responsible. In Drosophila, we found that the proliferation of neural stem cells, which generate all neurons and glia, is remarkably resistant to a wide range of metabolic stresses including nutrient restriction, hypoxia and oxidative stress. Sparing neural proliferation during stress involves key interactions between neural stem cells, their progeny neurons and also glia of the niche and blood-brain barrier. Some intercellular interactions required for brain sparing are mediated via receptor tyrosine kinase signalling and others via lipid metabolism and transport. In order to understand brain sparing with greater precision, we are actively developing new instruments for imaging metabolism at single-cell resolution.