title: A genome-wide survey of sexually dimorphic expression of Drosophila miRNAs identifies the steroid hormone-induced miRNA let-7 as a regulator of sexual identity.
abstract: MiRNAs bear an increasing number of functions throughout development and in the aging adult. Here we address their role in establishing sexually dimorphic traits and sexual identity in male and female Drosophila. Our survey of miRNA populations in each sex identifies sets of miRNAs differentially expressed in male and female tissues across various stages of development. The pervasive sex-biased expression of miRNAs generally increases with the complexity and sexual dimorphism of tissues, gonads revealing the most striking biases. We find that the male-specific regulation of the X chromosome is relevant to miRNA expression on two levels. First, in the male gonad, testis-biased miRNAs tend to reside on the X chromosome. Second, in the soma, X-linked miRNAs do not systematically rely on dosage compensation. We set out to address the importance of a sex-biased expression of miRNAs in establishing sexually dimorphic traits. Our study of the conserved let-7-C miRNA cluster controlled by the sex-biased hormone ecdysone places let-7 as a primary modulator of the sex-determination hierarchy. Flies with modified let-7 levels present doublesex-related phenotypes and express sex-determination genes normally restricted to the opposite sex. In testes and ovaries, alterations of the ecdysone-induced let-7 result in aberrant gonadal somatic cell behavior and non-cell-autonomous defects in early germline differentiation. Gonadal defects as well as aberrant expression of sex-determination genes persist in aging adults under hormonal control. Together, our findings place ecdysone and let-7 as modulators of a somatic systemic signal that helps establish and sustain sexual identity in males and females and differentiation in gonads. This work establishes the foundation for a role of miRNAs in sexual dimorphism and demonstrates that similar to vertebrate hormonal control of cellular sexual identity exists in Drosophila.
authors: Howard Hughes Medical Institute, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 fagegalt@cshl.edu halyna.shcherbata@mpibpc.mpg.de.
authors: Delphine
authors: D
authors: Fagegaltier
authors: Max Planck Research Group of Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
authors: Annekatrin
authors: A
authors: König
authors: Howard Hughes Medical Institute, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors: Assaf
authors: A
authors: Gordon
authors: Department of Developmental Biology, Sloan-Kettering Institute, New York, New York 10065.
authors: Eric C
authors: EC
authors: Lai
authors: Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors: Thomas R
authors: TR
authors: Gingeras
authors: Howard Hughes Medical Institute, Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724.
authors: Gregory J
authors: GJ
authors: Hannon
authors: Max Planck Research Group of Gene Expression and Signaling, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany fagegalt@cshl.edu halyna.shcherbata@mpibpc.mpg.de.
authors: Halyna R
authors: HR
authors: Shcherbata
mesh_terms: D000818:Animals; D002460:Cell Line; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D026461:Ecdysteroids / Q000502:physiology*; D005260:Female; D049750:Genome, Insect; D008221:Lymphoid Tissue / Q000166:cytology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D010053:Ovary / Q000378:metabolism; D034622:RNA Interference; D012727:Sex Characteristics; D019849:Sex Determination Processes; D013737:Testis / Q000378:metabolism; D015533:Transcriptional Activation; D059467:Transcriptome
chemical_list: D026461:Ecdysteroids; C531976:Let-7 microRNA, Drosophila; D035683:MicroRNAs
keywords: Drosophila; development; ecdysteroid; genetics of sex; gonad; miRNA; sex determination