Let-7-complex microRNAs regulate the temporal identity of Drosophila mushroom body neurons via chinmo.
Many neural lineages display a temporal pattern, but the mechanisms controlling the ordered production of neuronal subtypes remain unclear. Here, we show that Drosophila let-7 and miR-125, cotranscribed from the let-7-Complex (let-7-C) locus, regulate the transcription factor chinmo to control temporal cell fate in the mushroom body (MB) lineage. We find that let-7-C is activated in postmitotic neurons born during the larval-to-pupal transition, when transitions among three MB subtypes occur. Loss or increase of let-7-C delays or accelerates these transitions, respectively, and leads to cell fate transformations. Consistent with our identification of let-7 and miR-125 sites in a recently identified ∼6 kb extension of the chinmo 3' UTR, Chinmo is elevated in let-7-C mutant MBs. In addition, we show that let-7-C acts upstream of chinmo and that let-7-C phenotypes are caused by elevated chinmo. Thus, these heterochronic miRNAs, originally identified in C. elegans, underlie progenitor cell multipotency during the development of diverse bilateria.
Department of Biology, Indiana University, Bloomington, IN 47405, USA.
Yen-Chi
YC
Wu
Ching-Huan
CH
Chen
Adam
A
Mercer
Nicholas S
NS
Sokol
D000818:Animals; D019070:Cell Lineage / Q000502:physiology; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D056426:Genetic Loci; D035683:MicroRNAs / Q000502:physiology*; D024521:Mushroom Bodies / Q000166:cytology* / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*
C515167:Chinmo protein, Drosophila; D029721:Drosophila Proteins; C531976:Let-7 microRNA, Drosophila; C531977:MIRN125 microRNA, Drosophila; D035683:MicroRNAs; D009419:Nerve Tissue Proteins