There are a lot of situations in life where the “middleman” is unnecessary and costly. In cells, that middleman is necessary and fascinating at the same time. The sequence of DNA to middleman mRNA to protein provides our cells with countless ways to regulate complex events, including those surrounding stem cell divisions.
When stem cells divide, one daughter cell maintains stem cell characteristics while the other daughter cell follows a path towards differentiation. Before differentiation, this cell can divide several times during a stage called transit-amplification. In the fruit fly testes, the division of the germline stem cell (GSC) produces another GSC and transit-amplifying cells called spermatogonial cells. Spermatogonial cells begin differentiating as they pass through the spermatocyte stage on their way to becoming sperm. A recent paper in the journal Development investigates the regulation of a key differentiation factor, Bam (Bag of marbles), during this transition. Bam protein is found in spermatogonial cells, but is not found in the later spermatocyte stage (yet bam mRNA is present). According to Eun and colleagues, post-transcriptional regulation of Bam levels occurs through microRNA binding at the bam 3’UTR. Overexpression of the two microRNAs involved delayed the proliferation-to-differentiation transition, while failure of Bam down-regulation caused differentiation problems leading to male sterility. The images above show fruit fly testes stained to show the GSC hub (small red hub), spermatocytes (green) and Bam protein (red, white in inset images). In a control testis (left), Bam protein is found in spermatogonial cells near the GSCs. When the bam 3’UTR sequence was replaced with the 3’UTR of a constitutively expressed tubulin gene, Bam protein is found throughout spermatocytes as well.
Eun, S., Stoiber, P., Wright, H., McMurdie, K., Choi, C., Gan, Q., Lim, C., & Chen, X. (2012). MicroRNAs downregulate Bag of marbles to ensure proper terminal differentiation in the Drosophila male germline Development, 140 (1), 23-30 DOI: 10.1242/dev.086397