Steroid-induced microRNA let-7 acts as a spatio-temporal code for neuronal cell fate in the developing Drosophila brain. Mariya M. Kucherenko, Halyna R. Shcherbata. MPRG of Gene expression and signaling, Max Planck Institute for biophysical chemistry, Goettingen, Germany.

   Cell fate decisions are determined by an activation and repression of lineage-specific genes. In this context microRNAs (miRNAs), small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level, are important factors that maintain the balance between stem cell self-renewal, proliferation and differentiation during embryonic development and adult life. We found that in the post-embryonic Drosophila brain, cell fate of late-born neurons in the mushroom body, a brain region critical for olfactory learning and memory is regulated by the miRNA let-7 that is expressed in response to developmentally regulated steroid pulses. More specifically, ecdysteroid-induced miRNA let-7 controls the neuronal switch from / to / neurons that happens at the prepupal to pupal stage, which is one of many changes occurring at this developmental transition regulated by ecdysone signaling. let-7 is required cell autonomously for proper differentiation of the last-born / neurons and its deficiency leads to / lobe morphological defects that affect olfactory learning and memory. The cellular effect of steroid-hormone-induced let-7 expression is a modulation of levels of the cell adhesion molecule Fasciclin II (Fas II) in differentiating neurons partially via a posttranscriptional regulation of the transcription factor Abrupt (Ab) that we show to be a key factor for establishing / neuron identity. The differential adhesion hypothesis helps to explain how neurons that express different levels of cell adhesion proteins cluster and form complex internal brain structures, e.g. Drosophila mushroom bodies. Taken together, our data demonstrate that the miRNA let-7 is a steroid hormone-dependent cell fate determinant serving as a temporal code along with spatially controlled lineage cues to specify neuronal cell fate.