Article

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

Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Dr Bohr Gasse 3, 1030 Vienna, Austria.
Nature (impact factor: 36.28). 08/2008; 454(7201):241-5. DOI:10.1038/nature07014 pp.241-5
Source: PubMed

ABSTRACT Drosophila neuroblasts and ovarian stem cells are well characterized models for stem cell biology. In both cell types, one daughter cell self-renews continuously while the other undergoes a limited number of divisions, stops to proliferate mitotically and differentiates. Whereas neuroblasts segregate the Trim-NHL (tripartite motif and Ncl-1, HT2A and Lin-41 domain)-containing protein Brain tumour (Brat) into one of the two daughter cells, 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 4 transit-amplifying divisions to form a cyst of 16 interconnected cells that reduce their rate of growth and stop to proliferate mitotically. Here we show that the Trim-NHL protein Mei-P26 (refs 7, 8) restricts growth and proliferation in the ovarian stem cell lineage. Mei-P26 expression is low in stem cells but is strongly induced in 16-cell cysts. In mei-P26 mutants, transit-amplifying cells are larger and proliferate indefinitely leading to the formation of an ovarian tumour. Like brat, mei-P26 regulates nucleolar size and can induce differentiation in Drosophila neuroblasts, suggesting that these genes act through the same pathway. We identify Argonaute-1, a component of the RISC complex, as a common binding partner of Brat and Mei-P26, and show that Mei-P26 acts by inhibiting the microRNA pathway. Mei-P26 and Brat have a similar domain composition that is also found in other tumour suppressors and might be a defining property of a new family of microRNA regulators that act specifically in stem cell lineages.

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Keywords

16-cell cysts
 
cell biology
 
cell lineages
 
cell niche
 
common binding partner
 
daughter cell looses niche contact
 
daughter cell self-renews
 
defining property
 
extracellular signal
 
limited number
 
Lin-41 domain)-containing protein Brain tumour
 
Mei-P26 acts
 
microRNA pathway
 
new family
 
RISC complex
 
similar domain composition
 
transit-amplifying cells
 
Trim-NHL protein Mei-P26
 
tumour suppressors
 
two daughter cells