In Nature Methods from July, Xi Long and colleagues from the Howard Hughes Medicale Institute Janelia Research Campus (Ashburn, Virginia, USA) have developed a RNA fluorescence in situ hybridization (FISH) to study brain development and function, which require the expression of select genes at specific times in appropriate neurons.

We describe a fluorescence in situ hybridization method that permits detection of the localization and abundance of single mRNAs (smFISH) in cleared whole-mount adult Drosophila brains. The approach is rapid and multiplexable and does not require molecular amplification; it allows facile quantification of mRNA expression with subcellular resolution on a standard confocal microscope. We further demonstrate single-mRNA detection across the entire brain using a custom Bessel beam structured illumination microscope (BB-SIM).

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