Muscle niche-driven Insulin-Notch-Myc cascade reactivates dormant Adult Muscle Precursors in Drosophila

Muscles experience wear and tear over our lifetimes and therefore need to be regularly repaired and replenished by new cells. These cells are produced by stem cells, which often reside in a special microenvironment called the stem cell niche. This niche may also contain support cells that produce signals to attract stem cells and then maintain them in a dormant state. When the muscle is damaged, its resident stem cells are activated so that they divide to produce new cells. Understanding how this happens is an important goal for regenerative medicine, but many of the details remain unclear. In fruit flies, stem cells called adult muscle precursor cells (or AMPs for short) lie dormant in the embryo and larva, but are then activated to form the muscles of the adult fly. These cells share many features with the muscle stem cells of mammals, which prompted Aradhya, Zmojdzian et al. to use them as a model to investigate how stem cells find their niche and are later activated. For the experiments, the AMPs in fruit fly larvae were labelled with a fluorescent protein. Aradhya, Zmojdzian et al. observed that these cells produce long extensions that connect them to each other, to nearby muscle and to nerve cells. During development, these extensions are gradually lost until they contact only the muscles that are closest to the AMPs, which indicates that these muscles provide a niche for the AMPs and are perhaps involved in their activation. Further experiments show that neighbouring muscles do indeed help to activate AMPs, as they produce a signal that activates a cell communication system called the insulin pathway inside the AMPs. Insulin signalling – which is sensitive to the availability of nutrients in the body – turns on another signalling pathway, called Notch, that then stimulate the AMPs to divide. Aradhya, Zmojdzian et al. propose that this signalling cascade might help to ensure that AMPs are only activated at the right time in development. The next step is to find out whether stem cells in human muscles are activated in a similar way.