biostudies-literatureNarbonne-Reveau KLigue Contre le CancerAgence Nationale de la RechercheNIH HHSe1011680https://www.ebi.ac.uk/biostudies/studies/S-EPMC12064045biostudies-literatureUnknown21(4)MicroRNAs are essential regulators of gene expression. Their function is particularly important during neurogenesis, when the production of large numbers of neurons from a limited number of neural stem cells depends on the precise control of determination, proliferation and differentiation. However, microRNAs can target many mRNAs and vice-versa, raising the question of how specificity is achieved to elicit a precise regulatory response. Here we introduce in vivo AGO-APP, a novel approach to purify Argonaute-bound, and therefore active microRNAs from specific cell types. Using AGO-APP in the larval Drosophila central nervous system, we identify a module of microRNAs predicted to redundantly target all iconic genes known to control the transition from neuroblasts to neurons. While microRNA PLoS geneticsIn vivo AGO-APP identifies a module of microRNAs cooperatively preserving neural progenitors.PMC12064045) (MicroRNAct, ANR-17-CE16-0025; Uncoding, ANR-21-CE16-0034; Miniature, ANR-21-CE13-0003; Goligo, ANR-21-CE16-0023) and the Fondation pour la Recherche Médicale (Program Equipe FRM)programme Equipe LabelliséeP40 OD018537Erni ABeclin CCremer HMaurange CKapoor SNarbonne-Reveau KEichner NSankar SMeister GfalseIn vivo AGO-APP identifies a module of microRNAs cooperatively preserving neural progenitors.MicroRNAs are essential regulators of gene expression. Their function is particularly important during neurogenesis, when the production of large numbers of neurons from a limited number of neural stem cells depends on the precise control of determination, proliferation and differentiation. However, microRNAs can target many mRNAs and vice-versa, raising the question of how specificity is achieved to elicit a precise regulatory response. Here we introduce in vivo AGO-APP, a novel approach to purify Argonaute-bound, and therefore active microRNAs from specific cell types. Using AGO-APP in the larval Drosophila central nervous system, we identify a module of microRNAs predicted to redundantly target all iconic genes known to control the transition from neuroblasts to neurons. While microRNA 2025-01-01T00:00:00Z2025 Apr2026-07-07T03:16:02.465Z2026-07-07T03:08:30.532ZS-EPMC120640454029999710.1371/journal.pgen.1011680