Jumping genes cause tumour in fruit flies
The Btk enzyme, which plays an important part in human immune-cell signalling, regulates the formation of egg cells in the fruit fly, according to a new study in the scientific journal Science. If the enzyme does not inhibit transposable DNA elements called jumping genes, a tumour is formed instead of normal eggs.
The present study was a joint undertaking by the research groups at Karolinska Institutet and Tohoku University Graduate School of Life Sciences (Japan) that cloned the Btk gene in the human and fruit fly respectively. Mutations in Btk in humans give rise to a rare immunodeficiency disorder, X-linked agammaglobulinemia. The Btk gene codes for an enzyme that transduces signals from the cell membrane into the cell.
Patients lacking the enzyme are unable to manufacture antibodies, since the immune cells that produce them cannot develop. The corresponding gene in the fruit fly can also be mutated, but with a completely different outcome to that found in humans. Previous studies have shown, for example, that the flies die earlier as their lifespan is reduced to only 15 per cent of normal.
In the present study, the investigators have demonstrated that Btk-mediated signalling is also essential to the production of egg cells in the fruit fly. The lack of Btk disrupts the process so severely that fly is rendered unable to produce mature eggs and develops tumours instead.
"Instead of normal eggs, the germ cells develop into a kind of tumour," says research team member Edvard Smith at Karolinska Institutet's Department of Laboratory Medicine. This is extremely interesting since the production of eggs in the fruit fly takes place in one of the most well-studied biological stem cell niches there is. We've now been able to show how jumping genes, by which we mean transposable DNA sequences, are silenced by the Drosophila Btk, and if this doesn't occur, then the flies develop this tumour instead."
Interest in Btk was revived recently when it was shown that the protein also plays a key part in different forms of blood cancer originating in immune cells. A new Btk-inhibitor was recently approved for the treatment of leukaemia and lymphoma.
The study was financed by grants from several bodies, including the Swedish Cancer Society, the Swedish Research Council and the Stockholm County Council (ALF).
Text: Karin Söderlund Leifler
Publication
Btk29A promotes Wnt4 signaling in the niche to terminate germ cell proliferation in Drosophila.
Science 2014 Jan;343(6168):294-7