The larval-to-pupal onset of let-7-Complex microRNAs regulates chinmo to specify neuronal temporal identity. Nicholas S. Sokol, Yen-Chi Wu. Dept Biol, Indiana Univ, Bloomington, IN.

   Drosophila neural progenitors generate lineages composed of distinct neuronal subtypes. We find that the let-7-Complex (let-7-C) locus promotes the transitions in the production of these distinct subtypes in the post-embryonic mushroom body (MB) lineage, and are investigating whether let-7-C expression is linked to the embryonic temporal transcription factor (TTF) cascade in additional lineages throughout the nervous system. The let-7-C locus encodes three microRNAs (miR-100, let-7 and miR-125) and is transcriptionally activated in post-mitotic MB neurons during the larval-to-pupal transition, when three distinct MB subtypes (, pioneer , and neurons) are born. Loss or increase of let-7-C delays or accelerates the rate of transitions between these three subtypes, respectively, and lead to cell fate transformations. We speculated that chinmo may be a target of let-7-C microRNAs, since specification of these subtypes involves the post-transcriptional repression of chinmo. Consistent with this hypothesis, we find that the chinmo 3UTR contains functional let-7 and miR-125 binding sites and detect elevated levels of Chinmo protein in let-7-C MB cells. Furthermore, genetic interactions indicate that let-7-C mutant MB phenotypes are caused by elevated chinmo. Chinmo expression is modulated throughout the nervous system by the transient redeployment of two TTF genes, castor and seven-up, suggesting let-7-C may generally function as an intermediary for TTF mediated-chinmo regulation. To investigate the relationship between let-7-C and the TTF cascade, we have been characterizing in detail the onset of let-7-C in the adult lineages of the ventral nerve cord. Current experiments are directed at testing whether let-7-C onset is affected by the loss or overexpression of TFF components, including Hunchback, Kruppel, Pdm, Castor, Grainyhead, and Seven-Up. Taken together, these studies identify let-7-Complex microRNAs as critical components of a regulatory pathway that controls temporal identity during Drosophila nervous system development.