Movements such as the beating of heart, breathing and running etc. require considerable variation in the design of the muscles in terms of shape, size and position in the same animal. However, what controls this variation is an open question requiring investigation. In this latest study, the researchers have shown that, in the fruit fly Drosophila melanogaster, an equivalent set of adult muscle precursors (AMP’s) present at the early stages of development adopt different modes of division later in life to form diverse group of flight muscles. The progenitor cells initially divide exponentially and subsequently, in response to signaling from the neighbouring epidermal cells, transition to an asymmetric mode of cell division, giving rise to a heterogeneous cell population consisting of stem cells and post-mitotic muscle precursor cells. The disc-associated muscle progenitor cells have been established as a novel muscle stem cell population that orchestrates the early phases of adult flight muscle development.

The prevalent notion was that the cells exhibit a random pattern of division. However, the recent work unravels a pattern of cellular proliferation distinct from the previously held model. To identify the cellular mechanism of this extraordinary amplification, a very sophisticated genetic technique called the Twin-Spot MARCM was utilized in the study. This technique allows dual colour labeling of the daughter cells derived from the precursor myoblast, providing ability to trace the myogenic lineage, and identify the mode of cell division. The clones at early developmental stage had equal numbers of cells compared to unequal size of clones seen at late larval stages. The unequal clones consisting of a single elongated cell labeled in red and rest in green was indicative of stem cell like myoblasts having self renewing capacity. Previous researchers from the lab have been trying to identify stem cells using various other methods, but this latest technique was a breakthrough in nailing down the detection of stem cells present during the development of flight muscles in Drosophila.

Earlier work from the VijayRaghavan laboratory established a substantial understanding of epidermal signaling in various other contexts and demonstrated specific requirements for these pathways in determining the number of muscle progenitors. To begin with the authors used phosphor-histone-3 (PH3) staining, to determine the mitotic activity of the AMP’s. The majority of self renewing, proliferating myoblasts were seen at the layer close to the epithelium, while the post mitotic cells were found to be located at the distal layer. By perturbing members of different signaling pathways operating in the epidermal cells, Rajesh Gunage, the first author of the paper found that Notch and Wingless pathway are operating in this context. The two phase myogenic cell proliferation is regulated by signaling from the epidermal cells of the wing imaginal disc. The authors find that Serrate present at the epidermal niche during early larval stage leads to the activation of Notch signaling in the myoblasts responsible for symmetrical cell proliferation. While the subsequent Wingless signaling from notal region leads to the expression of Numb, which inhibits Notch in the myogenic population, generating asymmetric clones. The authors believe that this transition from symmetric to asymmetric proliferation could be a general strategy for generating a large number of differentiated cells from a small number of progenitors.