PT  - JOURNAL ARTICLE
AU  - Qian Dong
AU  - Michael Zavortink
AU  - Francesca Froldi
AU  - Sofya Golenkina
AU  - Tammy Lam
AU  - Louise Y. Cheng
TI  - Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in <em>Drosophila</em>
AID  - 10.1101/2020.05.18.100990
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.05.18.100990
4099  - http://biorxiv.org/content/early/2020/09/23/2020.05.18.100990.short
4100  - http://biorxiv.org/content/early/2020/09/23/2020.05.18.100990.full
AB  - The final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.Competing Interest StatementThe authors have declared no competing interest.