MicroRNA-9a (miR-9a) is involved in the rumble to regulate neurogenesis, a recent paper in Genes & Development shows. In Drosophila melanogaster, sensory organ precursors (SOPs) — which go on to generate sensory organs and neurons — develop from cells with the highest proneural gene expression. Until recently, it was thought that positive feedback generated by senseless (sens) coupled with lateral inhibition mediated by Notch and Delta was enough to generate differential proneural gene expression and SOP development. But the Gao group now shows that miR-9a offers a new layer of regulation — miR-9a regulates sens expression through its 3′ untranslated region (3′ UTR) and ensures the precise specification of SOPs.

Gao and colleagues first generated miR-9a-deficient D. melanogaster strains. These strains were viable and fertile, but larvae and adults had an abnormal morphology. Roughly 40% of mutant larvae had additional sensory neurons that were derived from SOPs. Similarly, ∼40% of mutant adults had additional sensory bristles on their anterior wing margins, ∼15% had additional sensory organs on their notums, and 100% had posterior wing margin defects. By contrast, flies that overexpressed miR-9a had markedly reduced numbers of sensory organs on both their wings and their notums.

Interestingly, the wing margin phenotype of flies that were deficient in miR-9a was similar to that of flies with a gain-of-function mutant of sens and that of flies in which sens was overexpressed. High-resolution in situ hybridization in the wings of control flies showed that miR-9a is not expressed in SOPs, and in vivo immunostaining of the dorsal region of the wing and the notum showed that overexpression of miR-9a corresponded with suppressed expression of sens.

To further investigate the relationship between sens and miR-9a, the 3′ UTR of sens was placed downstream of a reporter gene. Strikingly, co-expression of this construct with mi9-Ra reduced the expression of the reporter gene by 70%. So, in cells that are not destined to become SOPs, miR-9a inhibits residual sens expression by binding its 3′ UTR, thereby preventing proneural gene expression and SOP development.

But, it seems unlikely that miR-9a functions as an absolute switch; only a proportion of miR-9a-deficient flies developed additional sensory organs. The authors propose that miR-9a functions to fine-tune sens expression and the proneural gene feedback loop, thereby ensuring the precision of the production of SOPs. Intriguingly, miR-9a is 100% conserved from flies to humans, and miR-9a is highly expressed in neurogenic regions in the developing and adult mammalian brain. Perhaps, the authors note, miR-9a is also involved in mammalian neurogenesis.