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September 5th, 2025
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Universiteit Utrecht
developmental biology
bioRxiv

LGL-1 and the RhoGAP protein PAC-1 redundantly control polarization of the C. elegans embryonic epidermal epithelium

Jarosinska, O. D.Open in Google Scholar•Riga, A.Open in Google Scholar•Zahreddine Fahs, H.Open in Google Scholar•Woeltjes, J. M.Open in Google Scholar•Schmidt, R.Open in Google Scholar•Refai, F.Open in Google Scholar•Gopinadhan, S.Open in Google Scholar•Gunsalus, K.Open in Google Scholar•Boxem, M.Open in Google Scholar

The formation of an apical-basal axis of polarity is essential for the organization and functioning of epithelial cells. Apical-basal polarity is established by cortical polarity proteins that define the apical, junctional, and basolateral domains. While cortical polarity proteins are highly conserved and present in most epithelia, the mechanisms that establish polarity and the requirements for canonical polarity factors can vary between tissues and organisms. For example, the basolateral polarity protein lethal giant larvae (Lgl) is essential for the polarization of most Drosophila epithelia, yet is dispensable for epithelial polarization and viability in C. elegans. To better understand the epithelial polarity program in C. elegans, we performed a whole-genome RNAi screen for synthetic lethality with an lgl-1 deletion mutant. We found that combined loss of LGL-1 and the RhoGAP protein PAC-1 (RhoGAP19D in flies) leads to embryonic lethality due to defects in elongation and rupturing of the epidermis. We observed mislocalization of junctional proteins to the lateral domain of epidermal cells, presumably weakening tissue integrity. Furthermore, we observed expansion of the apical domain, sporadic aPKC mislocalization, and localization of the basolateral polarity protein LET-413Scribble in patches surrounded by DLG-1Discs large. These observations indicate that the combined loss of LGL-1 and PAC-1 leads to an overactivity of apical domain specifying factors. Consistent with this, partial inactivation of the apical polarity regulators aPKC or CDC-42 reduced the lethality of pac-1(RNAi); lgl-1(null) animals. Taken together, our findings identify pac-1 and lgl-1 as redundant inhibitors of apical polarity factors. While their relative contribution to the epithelial polarity program differ from fly epithelia, the canonical apical-basal polarity machinery is thus active in the embryonic epidermis of C. elegans - providing new insight into how conserved mechanisms are adapted across species.

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