PHRED-1 Is A Divergent Neurexin-1 Homolog That Organizes Muscle Fibers And Patterns Organs During Regeneration

Abstract

Regeneration of body parts requires the replacement of multiple cell types. To dissect this complex process, we utilized planarian flatworms that are capable of regenerating any tissue after amputation. An RNAi screen for genes involved in regeneration of the pharynx identified a novel gene, Pharynx regeneration defective-1 (PHRED-1) as essential for normal pharynx regeneration. PHRED-1 is a predicted transmembrane protein containing EGF, Laminin G, and WD40 domains, is expressed in muscle, and has predicted homologs restricted to other lophotrochozoan species. Knockdown of PHRED-1 causes abnormal regeneration of muscle fibers in both the pharynx and body wall muscle. In addition to defects in muscle regeneration, knockdown of PHRED-1 or the bHLH transcription factor MyoD also causes defects in muscle and intestinal regeneration. Together, our data demonstrate that muscle plays a key role in restoring the structural integrity of closely associated organs, and in planarians it may form a scaffold that facilitates normal intestinal branching.\n\nGraphical Abstract\n\nHighlights-PHRED-1 is a predicted transmembrane protein that contains Laminin G, EGF and WD40 domains\n\n-PHRED-1 is required for normal muscle patterning during regeneration\n\n-phred-1 is expressed in muscle cells\n\n-Muscle forms an essential scaffold for regeneration