miR-184 modulates dilp8 to control developmental timing during normal growth conditions and in response to developmental perturbations

Abstract

Organismal development depends on the precise coordination of growth and developmental timing, which is regulated by a complex interplay of intrinsic and extrinsic factors. However, the mechanisms underlying this regulation are not fully understood. Post-transcriptional regulation by microRNAs (miRNAs) plays a pivotal role in ensuring the proper timing of gene expression necessary for growth and development. In this study, we conducted a genetic screen to identify microRNAs that regulate developmental timing in Drosophila. Our screen identified miR-184, previously implicated in germline maturation and embryonic development, as a regulator of pupariation timing by acting in the larval imaginal discs. Using genetic and molecular approaches, we identified Drosophila insulin-like peptide 8 (Dilp8), a paracrine factor critical for regulating developmental stability, as a target of miR-184. During normal larval development miR-184 facilitates timely pupariation by regulating dilp8 levels. Furthermore, we demonstrate that miR-184 plays a critical role in tissue damage responses by inducing dilp8 expression, which delays pupariation to enable damage repair mechanisms. These findings reveal a novel post-transcriptional regulatory mechanism that links miR-184 to the control of developmental timing under normal growth conditions and in response to tissue damage.