Makorin 1 Regulates Developmental Timing in Drosophila

The central mechanisms coordinating growth and sexual maturation are well conserved across invertebrates and vertebrates. Although mutations in the gene encoding makorin RING finger protein 3 (mkrn3 ) are associated with central precocious puberty in humans, a causal relationship has not been elucidated. Here, we examined the role of mkrn1, a Drosophila ortholog of mammalian makorin genes, in the regulation of developmental timing. Loss of MKRN1 in mkrn1(exS) prolonged the 3(rd) instar stage and delayed the onset of pupariation, resulting in bigger size pupae. MKRN1 was expressed in the prothoracic gland, where the steroid hormone ecdysone is produced. Furthermore, mkrn1(exS) larvae exhibited reduced mRNA levels of phantom, which encodes ecdysone-synthesizing enzyme and E74, which is a downstream target of ecdysone. Collectively, these results indicate that MKRN1 fine-tunes developmental timing and sexual maturation by affecting ecdysone synthesis in Drosophila. Moreover, our study supports the notion that malfunction of makorin gene family member, mkrn3 dysregulates the timing of puberty in mammals.