21 Oral - Neurodevelopment I
Thursday April 07, 5:45 PM - 6:00 PM

Authors:
Eva Islimye; Victor Girard; Andrew Bailey; Alex P. Gould

Affiliation: The Francis Crick Institute, London, UK

Keywords:
o. stem cells; a. stress responses

During development, multipotent neural stem cells proliferate within a specialised local microenvironment called the niche. Work in Drosophila and mammals has shown that lipid metabolism is important for regulating the divisions of neural stem cells. During Drosophila development, the proliferation of stem/progenitor cells is more protected from hypoxia and oxidative stress in the central nervous system (CNS) than in other tissues. We previously found that the biosynthesis of lipid droplets (LDs) in glia of the neural stem cell niche functions to protect against lipid peroxidation — not only in the glia themselves but also in neighbouring neural stem cells (neuroblasts). Using labelled fatty acids and cell type-specific genetic manipulations, we now investigate the origin of the lipid cargo in the triacylglycerol (TAG) core of glial LDs. We present evidence that oxidative stress triggers neurons to release fatty acids via a process that requires functional mitochondria. Extracellular fatty acids are then taken up by glia and directed towards the TAG core of LDs. Diacylglycerol acyltransferase 1 (Dgat1/Mdy) and adipose triglyceride lipase (Atgl/Bmm) manipulations demonstrate that fatty acid flux through the TAG compartment of glia sustains neuroblast proliferation during oxidative stress. In contrast, fatty acid flux through the TAG compartment of neuroblasts inhibits proliferation during oxidative stress. The contrasting functions of TAG metabolism in glia and neuroblasts are consistent with a model whereby oxidative stress triggers neurons to release potentially toxic fatty acids that are then preferentially captured and processed in niche glia in order to safeguard neuroblast proliferation. Together, our findings reveal how lipid metabolic crosstalk between the three major cell types of the developing CNS functions to spare neural proliferation during oxidative stress.