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

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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.

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