Beat II and Side IV keep migrating longitudinal visceral muscle precursor cells on their substratum in Drosophila

The proper formation of tissues and organs relies on precisely regulated differentiation and migration processes. In Drosophila embryos, the development of the midgut musculature requires coordinated movement of caudal visceral mesoderm (CVM) cells across the trunk visceral mesoderm (TVM). Here, we report that Beaten path (Beat) II proteins (Beat IIa and Beat IIb) are specifically expressed in CVM cells, whereas Sidestep IV (Side IV) is expressed in their substrate, the TVM. Both beat II and side IV mutants show similar migration defects, characterized by irregular migration patterns and abnormal cell distributions. At the end of embryogenesis, the midgut contains areas devoid of longitudinal muscles, resulting in a reduced number of longitudinal muscle fibres at larval stages. In cell-cell aggregation assays, Beat II proteins specifically interact with Side IV in trans. Moreover, ectopic expression of Side IV in trachea attracts migrating CVM cells and aligns them along tracheal branches. Altogether, these findings suggest that Side IV and Beat II proteins likely act as a ligand-receptor pair, providing guidance signals to assist in the formation of longitudinal muscle fibres of the midgut.