Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation inDrosophila

Abstract

The final size of the adult central nervous system (CNS) is determined by the size of neuronal lineages generated by neural stem cells (NSCs) during development. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-cell autonomous regulation of NB behaviour by glia during normal development, and upon glial overgrowth. We show that lipid droplets that reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, Hh is present at low levels in the glial niche to ensure NBs faithfully produce the correct number and types of progeny that populate the adult nervous system. Upon Fibroblast Growth Factor (FGF) activation in glia, an accumulation of lipid droplets and Hh ligand non-cell autonomously triggers adjacent NBs to reduce their cell cycle speed, increase the developmental period in which they proliferate and disrupt their asymmetric division. Downstream of FGF signalling in the glia, we found that lipid metabolism affects both Hh subcellular localisation, as well as Hh post-translational modification, to modulate its activity, and in turn, its ability to activate Hh-signalling in the adjacent NBs. Together, our data suggest that wildtype and dysfunctional glial niche non-autonomously regulate neural lineage size via modulation of lipid metabolism and Hedgehog signalling. Statistical analysisP-values are calculated by two-tailed, unpaired Student's t-test, with equal sample variance; The Welch's correction was applied in case of unequal variances. Mann-Whitney test was used when data deviated from a normal distribution. For all histograms, error bars represent SEM.

A corset of adhesions during development establishes individual neural stem cell niches and controls adult behaviour

“…The blood-brain barrier forms the interface with the systemic environment, and controls NSC reactivation [14] and proliferation [15]. A specific glial subtype, the cortex glia (CG), is in close contact with NSCs and their progeny, and is crucial for NSC proliferation [16][17][18], resistance to stress [19,20] as well as for the survival of newborn neurons [21]. Remarkably, the CG form a continuous glial network which invades the whole CNS (Fig 1C-D) while building bespoke encasing of individual NSC lineages (comprising NSC, GMC and newborn neurons, as well as INP for Type II NSCs), called CG chambers [21][22][23].…”