A population of adult satellite-like cells in Drosophila is maintained through a switch in RNA-isoforms

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Abstract

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.

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All data generated or analysed during this study are included in the manuscript and supporting files

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Hadi Boukhatmi

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

Competing interests
The authors declare that no competing interests exist.
Sarah Bray

Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom

For correspondence
sjb32@cam.ac.uk

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-1642-599X

Funding

Medical Research Council (MRL007177/1)

Sarah Bray

European Molecular Biology Organization (ALTF-325-2013)

Hadi Boukhatmi

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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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.