Dynein directs prophase centrosome migration to control the stem cell division axis in the developing C. elegans epidermis

Abstract

The microtubule motor dynein is critical for the assembly and positioning of mitotic spindles. In C. elegans, these dynein functions have been extensively studied in the early embryo but remain poorly explored in other developmental contexts. Here we use a hypomorphic dynein mutant to investigate the motors contribution to asymmetric stem cell-like divisions in the larval epidermis. Live imaging of seam cell divisions that precede formation of the seam syncytium shows that mutant cells properly assemble but frequently mis-orient their spindle. Mis-oriented divisions misplace daughter cells from the seam cell row, generate anucleate compartments due to aberrant cytokinesis, and disrupt asymmetric cell fate inheritance. Consequently, the seam becomes disorganized and populated with extra cells that have lost seam identity, leading to fatal epidermal rupture. We show that dynein orients the spindle through the cortical GOA-1Gi-LIN-5NuMA pathway, which directs the migration of prophase centrosomes along the anterior-posterior axis. Spindle mis-orientation in the dynein mutant can be rescued by stretching cells, implying that dynein-dependent cortical cues and elongated cell shape jointly ensure correct asymmetric division of epithelial stem cells.