Genetic and Molecular Regulation of Ecdysone Biosynthesis During Insect Metamorphosis

Steroid hormones govern diverse physiological processes during juvenile-to-adult development across vertebrates and invertebrates, ranging from pubertal initiation in mammals to metamorphosis in insects. Ecdysteroids, the collective name for many moulting hormones in insects, act as master effectors driving metamorphic development. Their biosynthesis begins with dietary cholesterol as the direct precursor (phytosterols are converted as needed) and is driven by a series of enzymatic reactions catalyzed by the evolutionarily conserved Halloween genes to produce ecdysone, which is ultimately converted into its potent metabolite 20-hydroxyecdysone (20E) in target tissues to induce extensive morphological and physiological changes. The precise temporal pattern of molting and metamorphosis is dictated by periodic ecdysone surges originating from the prothoracic gland. Given the extensive utility of Drosophila as a major model organism for investigating systemic growth and developmental timing, this review synthesizes recent insights into the regulatory mechanisms underlying ecdysone biosynthesis. In this review, we begin by outlining the ecdysteroid biosynthetic cascade and core catalytic enzymes in the prothoracic gland, followed by a systematic discussion of diverse regulatory strata, encompassing substrate availability, transcriptional regulation and chromatin accessibility, and their vital contributions to the control of ecdysteroid production.