Mei-P26 regulates microRNAs and cell growth in the Drosophila ovarian stem cell lineage

Ralph A. Neumüller, Joerg Betschinger, Anja Fischer, Natascha Bushati, Ingrid Poernbacher, Karl Mechtler, Stephen M. Cohen and Juergen A. Knoblich ()
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Ralph A. Neumüller: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria
Joerg Betschinger: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria
Anja Fischer: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria
Natascha Bushati: European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany
Ingrid Poernbacher: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria
Karl Mechtler: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria
Stephen M. Cohen: European Molecular Biology Laboratory (EMBL), Meyerhofstraße 1, 69117 Heidelberg, Germany
Juergen A. Knoblich: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria

Nature, 2008, vol. 454, issue 7201, 241-245

Abstract: Ovarian stem cells: Mei-P26 regulates microRNAs In Drosophila ovarian stem cells, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Ovarian stem cells are regulated by an extracellular signal from the surrounding stem cell niche. After division, one daughter cell looses niche contact. It undergoes four transit amplifying divisions to form a cyst of 16 interconnected cells which reduce their rate of growth and stop to proliferate mitotically. This paper shows that the Trim-NHL protein Mei-P26 restricts growth and proliferation in the ovarian stem cell lineage. In mei-P26 mutants transit amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. In addition, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. They also show Mei-P26 binds to Argonaute-1, a component of the RISC complex, and they show that Mei-P26 acts by inhibiting the microRNA pathway. This work establishes Trim-NHL proteins as regulators of stem cell proliferation.

Date: 2008
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DOI: 10.1038/nature07014

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