Steroid-induced microRNA let-7 acts as a spatio-temporal code for neuronal cell fate in the developing Drosophila...

Mammalian neuronal stem cells produce multiple neuron types in the course of an individual's development. Similarly, neuronal progenitors in the Drosophila brain generate different types of closely related neurons that are born at specific time points during development. We found that in the post-embryonic Drosophila brain, steroid hormones act as temporal cues that specify the cell fate of mushroom body (MB) neuroblast progeny. Chronological regulation of neurogenesis is subsequently mediated by the microRNA (miRNA) let-7, absence of which causes learning impairment due to morphological MB defects. The miRNA let-7 is required to regulate the timing of α'/β' to α/β neuronal identity transition by targeting the transcription factor Abrupt. At a cellular level, the ecdysone-let-7-Ab signalling pathway controls the expression levels of the cell adhesion molecule Fasciclin II in developing neurons that ultimately influences their differentiation. Our data propose a novel role for miRNAs as transducers between chronologically regulated developmental signalling and physical cell adhesion.