Susumu Katsuma and colleagues have answered a question that has perplexed insect geneticists for more than eight decades — how does the W chromosome determine femaleness in the silkworm Bombyx mori and many other Lepidoptera? In this system, males have two Z sex chromosomes and females have one Z and one W. The authors show that the feminizing factor is a single W chromosome-derived PIWI-interacting RNA (piRNA). The piRNA silences the product of a gene located on the Z chromosome (named Masc) that encodes a CCCH-type zinc finger protein. This silencing is in turn important for the production of female-specific isoforms of the doublesex gene that acts at the downstream end of the sex differentiation cascade in the embryo. In male embryos Masc protein controls both dosage compensation and masculinization.
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