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Home | Pregnancy Timeline | News Alerts |News Archive Aug 26, 2014

Cold Spring Harbor Laboratory researchers found that miRNAs, short RNA molecules,
are responsible for sexual differences in fruit flies. Above: the testes of a male
fruit fly with an inactivated hormone. The abnormal testes fail to make sperm.
They now produce sex determinants (red) found in the ovaries of female flies.
Image Credit: D. Fagegaltier/ Cold Spring Harbor Laboratory

 






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microRNAs new basis for sex determination

Cold Spring Harbor Laboratory (CSHL) scientists have found a subset of very small genes, called microRNAs (miRNAs), play a key role in differentiating male and female tissues in the fruit fly.

In the past, most research has focused on understanding how genes that encode proteins act as sex determinants. But Cold Spring Harbor Laboratory (CSHL) scientists have found that a subset of very small genes, called microRNAs (miRNAs), also play a key role in differentiating male and female tissues in the fruit fly and possibly in humans as well.

A miRNA is a short segment of RNA that fine-tunes the activation of one or several protein-coding genes. miRNAs are able to silence the genes they target and, in doing so, orchestrate complex genetic programs that are the basis of development.

In work published in Genetics, a team of CSHL researchers and colleagues describe how miRNAs contribute to sexual differences in fruit flies.


You've probably never noticed, but male and female flies differ visibly, just like other animals. For example, females are 25% larger than males with lighter pigmentation and more abdominal segments.


The team of researchers, including Delphine Fagegaltier, PhD, lead author on the study, and CSHL Professor and Howard Hughes Medical Institute Investigator Greg Hannon, identified distinct miRNA populations in male and female flies.


"We found that the differences in miRNAs are important in shaping the structures that distinguish the two sexes. In fact, miRNAs regulate the very proteins that act as sex determinants during development.

"They send signals that allow germ cells, i.e., eggs and sperm, to develop, ensuring fertility. Removing one miRNA from mature, adult flies causes infertility. In a sense, once they have lost this miRNA, the flies become male and female at the same time.

"
It is amazing that the very smallest genes can have such a big effect on sexual identity."

Delphine Fagegaltier, PhD, lead author on the study.


The team found that miRNAs are essential for sex determination even after an animal has grown to adulthood.

Some miRNAs examined in the study, such as let-7, have been preserved by evolution because of their utility; humans and many other animals carry versions of them.


"This is probably just the tip of the iceberg. There are likely many more miRNAs regulating sexual identity at the cellular and tissue level, but we still have a lot to learn about these differences in humans, and how they could contribute to developmental defects and disease."

Delphine Fagegaltier, PhD


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.

The authors are: Delphine Fagegaltier, Annekatrin König, Assaf Gordon, Eric Lai, Thomas Gingeras, Gregory Hannon, and Halyna Shcherbata.

This work was supported by National Institute of Health, Max Planck Society, and a kind gift from the late Kathryn W. Davis.

About Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit http://www.cshl.edu.



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