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. Similar to vertebrates, Drosophila have a population of residual satellite cells (SCs) in adult muscles that retain characteristics of muscle progenitors. We have uncovered a role for zfh1, a Notch target, in keeping these progenitors/SCs undifferentiated. Their differentiation into functional muscles is accompanied by expression of a conserved micro RNA , mir-8/mir-200, which targets the major “long” zfh1 isoform and decrease Zfh1 protein. Importantly, an alternate, zfh1-short isoform is produced at high level in the SCs. Because short zfh1 lacks the target-site for mir-8, Zfh1 protein is maintained in SCs and they can escape differentiation. This type of regulatory logic, utilizing RNA isoforms with differential sensitivity to mIRs, may be of general relevance for progenitor maintenance in other tissues.