The BEN domain protein LIN-14 coordinates neuromuscular positioning during epidermal maturation

Development and function of an organism depend on coordinated inter-tissue interaction. How such interactions are maintained during tissue renewal and reorganization remains poorly understood. Here, we find that Caenorhabditis elegans BEN domain transcription factor LIN-14 is required in epidermis for maintaining the position of motor neurons and muscles during developmental tissue reorganization. lin-14 loss of function (lf) mutants display highly penetrant ventral neuromuscular mispositioning. These defects arise post-embryonically during first larval (L1) stage as the maturing epidermis replaces the embryonic ventral epidermis. Tissue-specific and temporally controlled depletion experiments indicate LIN-14 acts within the epidermis for ventral neuromuscular positioning. lin-14(lf) mutants show defects in formation of epidermis-muscle attachment complex hemidesmosomes in the maturing ventral epidermis, leading to detachment of muscles and motor neurons as well as movement defects. Our findings reveal a cell non-autonomous role for LIN-14 in coordinating inter-tissue interaction and neuromuscular positioning during epidermal maturation.