Apical-basal polarity is essential for epithelial organization and function and is established by conserved cortical polarity proteins. However, the requirements for canonical polarity factors vary between tissues and organisms. For example, the basolateral protein lethal giant larvae is essential for epithelial polarity in Drosophila but dispensable in Caenorhabditis elegans. To better define the epithelial polarity program in C. elegans, we performed a genome-wide RNAi screen for synthetic lethality with lgl-1. Combined loss of LGL-1 and the RhoGAP PAC-1 caused embryonic lethality due to elongation defects and epidermal rupture. Epidermal cells showed expansion of the apical domain and aPKC, accompanied by mislocalization of junctional proteins and LET-413Scribble. These defects indicate overactivity of apical polarity determinants. Consistently, partial inactivation of aPKC or CDC-42 suppressed lethality in pac-1; lgl-1 animals. Together, our results identify PAC-1 and LGL-1 as redundant inhibitors of apical polarity in the C. elegans embryonic epidermis and provide new insights into how conserved mechanisms are adapted across species.
Jarosińska et al. (2026) studied this question.