4.8 Article

Glia-derived temporal signals orchestrate neurogenesis in the Drosophila mushroom body

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2020098118

Keywords

glia; neurogenesis; mushroom body

Funding

  1. ShanghaiTech
  2. National Natural Science Foundation of China [31871039]

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The study uncovers how external glial-to-neuron communication coordinates with neuroblast proliferation capacity to regulate neurogenesis in the Drosophila mushroom body.
Intrinsic mechanisms such as temporal series of transcription factors orchestrate neurogenesis from a limited number of neural progenitors in the brain. Extrinsic regulations, however, remain largely unexplored. Here we describe a two-step glia-derived signal that regulates neurogenesis in the Drosophila mushroom body (MB). In a temporal manner, glial-specific ubiquitin ligase dSmurf activates non-cell-autonomous Hedgehog signaling propagation by targeting the receptor Patched to suppress and promote the exit of MB neuroblast (NB) proliferation, thereby specifying the correct alpha/beta cell number without affecting differentiation. Independent of NB proliferation, dSmurf also stabilizes the expression of the cell-adhesion molecule Fasciclin II (FasII) via its WW domains and regulates FasII homophilic interaction between glia and MB axons to refine alpha/beta-lobe integrity. Our findings provide insights into how extrinsic glia-to-neuron communication coordinates with NB proliferation capacity to regulate MB neurogenesis; glial proteostasis is likely a generalized mechanism in orchestrating neurogenesis.

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