NEUROGENESIS Food Signals Wake Sleeping Stem Cells Stem Cells in Neurogenic Areas of Insulin-Like Receptor (Inr)

ReseaRch highlights

NEUROGENESIS Food signals wake sleeping stem cells Stem cells in neurogenic areas of insulin-like receptor (InR). This sug- antagonizes PI3K — specifically in the adult mammalian brain are able gested that glial ILPs might activate neuroblasts. All three manipulations to switch between quiescence and the insulin signalling pathway in blocked neuroblast reactivation. proliferation, but what are the factors neuroblasts to induce reactivation. Conversely, neuroblasts expressing that trigger their reactivation? Chell In larvae, growth and cell prolif- a constitutively active form of the and Brand show that in Drosophila, eration are nutrition-dependent and PI3K catalytic subunit were able to neural stem cell reactivation is neuroblasts cannot reactivate if larvae reactivate in the absence of a nutri- induced by glial cells, which secrete are deprived of amino acids. The tional stimulus. Upregulating Akt, a insulin-like peptides (ILPs) in authors found that glial expression downstream component of the PI3K response to a nutritional stimulus. of ILP 2 and ILP6 was reduced in signalling pathway, was similarly able Insulin and insulin-like growth larvae fed an amino acid-free diet. In to trigger quiescent neuroblasts to factors (IGFs) are known to be major these larvae, neuroblast reactivation grow and start proliferating. These regulators of growth and metabolism, could be restored by glial-specific results indicate that activation of and the authors therefore set out overexpression of ILP2 or ILP6, the PI3K–Akt pathway is necessary to determine whether they are whereas disrupting glial signalling and sufficient to drive neuroblast involved in neural stem cell (by blocking vesicular trafficking) reactivation. reactivation. They used severely inhibited reactivation. Together, these findings suggest Drosophila as a model, ILPs bind to the insulin receptor, that in Drosophila, a nutritional as their neural stem thereby inducing the phosph- stimulus is transduced from glia cells (neuroblasts) oinositide 3-kinase (PI3K)–Akt to quiescent neuroblasts through undergo periods pathway. In neuroblasts entering the insulin-like signalling. This activates of quiescence and proliferation stage, the authors noted the PI3K–Akt signalling pathway in proliferation during high phosphatidylinositol-3,4,5- neuroblasts, triggering them to grow specific develop- trisphosphate (PIP3) levels at the and initiate proliferation. The results mental stages. membrane (suggestive of PI3K highlight the efficacy of targeting They found that activation). In larvae lacking the support (or niche) cells to manipulate at least two catalytic subunit of PI3K, neuroblasts the behaviour of stem cells. Future insulin-like remained quiescent, suggesting that research will establish whether mech- peptides PI3K signalling is required for anisms similar to those described in (ILP2 and neuroblast reactivation. Drosophila are at play in neurogenic ILP6) are To establish whether PI3K signal- areas of the mammalian brain. expressed by ling occurs intrinsically in neuro- Leonie Welberg glial cells blasts to induce their reactivation, the overlying authors expressed dominant-negative ORIGINAL RESEARCH PAPER Chell, J. M. & the quiescent forms of a PI3K subunit or InR, Brand, A. H. Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell 143, stem cells, which or high levels of phosphatase and 1161–1173 (2010) themselves express the tensin homologue (PTEN) — which