PgmNr D1218: Eyeless regulates nutrient-insensitive neuroblast proliferation in the central brain.

Authors:
Conor Sipe; Sarah Siegrist


Institutes
University of Virginia, Charlottesville, VA.


Keyword: neural stem cells

Abstract:

The genetically tractable neural stem cell (NSC) population in the Drosophila central brain is ideal for investigating how organismal nutritional status affects stem cell proliferation.  All neurons in the fly central brain are generated from asymmetric cell divisions of NSCs, known as neuroblasts (NBs). Most NBs enter a period of quiescence at the end of embyrogenesis coincident with declining maternal stores; upon larval feeding and reception of a nutrient-derived cue, these nutrient-sensitive NBs reenter the cell cycle and begin a second round of proliferation that continues until early pupal stages. In contrast, mushroom body (MB) NBs, a subset of central brain NBs, never enter quiescence and divide continuously regardless of developmental stage or systemic nutritional state. Both nutrient-sensitive NBs and nutrient-insensitive MB NBs reside in close proximity to one another, sharing a common brain macroenvironment. This suggests that quiescence versus proliferation decisions may be regulated in a cell-intrinsic manner. Currently, we are investigating whether the Drosophila Pax-6 ortholog, Eyeless (Ey) regulates NB quiescence versus proliferation in response to nutrient conditions. Ey, a paired box and homeodomain transcription factor, is expressed specifically in MB NBs and not in other central brain NBs during the embryo to larval transition. When Ey is knocked down in MB NBs, we observe that MB NBs, like other NBs, now enter quiescence when nutrients are limited. Importantly, we find that these quiescent MB NBs reactivate and re-enter the cell cycle once animals are returned to a complete diet. In addition, overexpression of Ey allows nutrient-sensitive non-MB NBs to maintain proliferation when nutrients are limited. This suggests that MB NBs utilize Ey to bypass quiescence during periods of nutrient restriction.  Taken together, these results identify a novel genetic program under the control of Ey that promotes neuroblast proliferation independent of systemic nutrient cues.



Flybase Genetic Index:
1. FlyBase gene symbol: ey; FBgn: FBgn0005558