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Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila

Qian Dong, Michael Zavortink, Francesca Froldi, Sofya Golenkina, Tammy Lam, Louise Y. Cheng
doi: https://doi.org/10.1101/2020.05.18.100990
Qian Dong
1Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Victoria, 3000
2Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010
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Michael Zavortink
1Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Victoria, 3000
2Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010
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Francesca Froldi
1Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Victoria, 3000
2Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010
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Sofya Golenkina
1Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Victoria, 3000
2Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010
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Tammy Lam
1Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Victoria, 3000
2Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010
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Louise Y. Cheng
1Peter MacCallum Cancer Centre, 305 Grattan St, Parkville, Victoria, 3000
2Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, Australia, 3010
3The Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia, 3010
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  • For correspondence: louise.cheng@petermac.org
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 23, 2020.
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Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila
Qian Dong, Michael Zavortink, Francesca Froldi, Sofya Golenkina, Tammy Lam, Louise Y. Cheng
bioRxiv 2020.05.18.100990; doi: https://doi.org/10.1101/2020.05.18.100990
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Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila
Qian Dong, Michael Zavortink, Francesca Froldi, Sofya Golenkina, Tammy Lam, Louise Y. Cheng
bioRxiv 2020.05.18.100990; doi: https://doi.org/10.1101/2020.05.18.100990

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