Amalgam plays a dual role in controlling the number of leg muscle progenitors and regulating their interactions with developing tendon

Formation of functional organs requires cell-cell communication between different cell lineages, and failure in this communication can result in severe developmental defects. Hundreds of possible interacting pairs of proteins are known, but identifying the interacting partners that ensure specific interaction between two given cell types remains challenging. Here we use the Drosophila leg model to uncover molecular mediators of cell-cell communications that ensure coordinated development between tendon and muscle precursors. By analyzing gene expression signatures of appendicular muscle and tendon precursor cells, we identify Amalgam (Ama ) and Neurotactin (Nrt) as candidates ensuring early interactions between these two cell populations. Ama encodes secreted proteins and is expressed in the leg myoblasts, whereas Nrt encodes membrane-bound proteins and is expressed in adjacent tendon precursors. In Ama and Nrt mutants, myoblast-tendon cell-cell association is lost, leading to tendon developmental defects. We also show that Ama acts downstream of the FGFR pathway to maintain the myoblast population by promoting cell survival and proliferation in a Nrt-independent manner. Together, our data characterize molecular actors in an early interaction between leg muscle and tendon precursors. These results demonstrate early reciprocal communication at the molecular level between two major components of the appendicular musculoskeletal system, ensuring specificity of myoblasts to tendon precursor association. ### Competing Interest Statement The authors have declared no competing interest.