Atypical soluble guanylyl cyclases control brain size in Drosophila.

Hypoxia-induced proliferation of neural stem cells has a crucial role in brain development. In the brain of Drosophila melanogaster , the optic lobe exhibits progressive hypoxia during larval development. Here, we investigate an alternative oxygen-sensing mechanism within this brain compartment, distinct from the canonical hypoxia signaling pathway mediated by HIF. Using genetic tools, immunostaining, and confocal microscopy, we demonstrate that the loss of the atypical soluble guanylyl cyclase (asGC) subunit Gyc88E , or the ectopic expression of Gyc89Db in neural stem cells leads to increased optic lobe volume. We propose the existence of a link between cGMP signaling and neurogenesis in the developing brain.