A study by Professor Hannele Ruohola-Baker, with Biochemistry graduate student Steve Hatfield as first author, was among three papers highlighted in the June 16, 2005 issue of Nature. This image from Hatfield et al. shows that stem cells lacking microRNAs stop dividing due to overproduction of the tumor suppressor p21/p27. The work was performed in collaboration with Professor Richard Carthew of Northwestern University. The regulatory functions of microRNAs in the process of stem cell division are one focus of the Ruohola-Baker group, which uses the fruit fly Drosophila as a model for human disease.

Reference

Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H (2005) Stem cell division is regulated by the microRNA pathway. Nature 435: 974-978.

Abstract

One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded Rnase III essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition. For more information visit the Ruohola-Baker Group Project page.

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