Adult stem cells are important for tissue maintenance and repair. One key question is how such cells are specified and then protected from differentiation for a prolonged period. Investigating the maintenance of Drosophila muscle progenitors (MPs) we demonstrate that it involves a switch in zfh1/ZEB1 RNA-isoforms. Differentiation into functional muscles is accompanied by expression of miR-8/miR-200, which targets the major zfh1-long RNA isoform and decreases Zfh1 protein. Through activity of the Notch pathway, a subset of MPs produce an alternate zfh1-short isoform, which lacks the miR-8 seed site. Zfh1 protein is thus maintained in these cells, enabling them to escape differentiation and persist as MPs in the adult. There, like mammalian satellite cells, they contribute to muscle homeostasis. Such preferential regulation of a specific RNA isoform, with differential sensitivity to miRs, is a powerful mechanism for maintaining a population of poised progenitors and may be of widespread significance.
- Sarah Bray
- Hadi Boukhatmi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Manfred Frasch, Reviewing Editor, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany
- Received: February 15, 2018
- Accepted: April 7, 2018
- Accepted Manuscript published: April 9, 2018 (version 1)
© 2018, Boukhatmi & Bray
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.