PgmNr D1228: Reactivation of Quiescent Neuroblasts Requires Activation of PI3-kinase Signaling in Cortex Glia.

Authors:
X. Yuan; S. Siegrist


Institutes
University of Virginia, Charlottesville, VA.


Keyword: niche and other local signaling

Abstract:

Precise timing of stem cell entry into and exit from quiescence is essential for tissue morphogenesis and homeostasis. Drosophila neuroblasts (NBs), the stem cells of the Drosophila CNS, provide a model for investigating regulation of stem cell quiescence.  At the end of embryogenesis, all NBs in the central brain, except for a subset, exit cell cycle and enter a period of quiescence. NBs exit quiescence and begin proliferating in response to a nutrient-derived cue received soon after larvae consume their first complete meal. NB exit from quiescence fails if larvae consume a meal that lacks amino acids. The current model posits that amino acids are required for the synthesis and secretion of Dilp6 in glia and that local production of Dilp6 in glia is required to reactivate quiescent NBs through activation of the highly conserved PI3-kinase growth signaling pathway in NBs. We are investigating whether amino acids are also required for glia growth, morphology, and subsequent ensheathment of NBs. When animals are fed a diet lacking amino acids, we find that the amount of glial membrane and growth is reduced compared to animals fed a complete diet. This reduction in glial growth is likely caused by a reduction in levels of PI3-kinase activity in glia in response to absence of dietary amino acids. NBs fail to exit from quiescence when dietary amino acids are absent or when PI3-kinase is reduced in glia. Currently, we are investigating whether nutrition first stimulates activation of PI3-kinase signaling in cortex glia, leading to glial growth and ensheathment of NBs, and whether glial ensheathment is required for NB exit from quiescence.



Flybase Genetic Index:
1. FlyBase gene symbol: Pi3K92E; FBgn: FBgn0015279