Mazzoli, S.; SONNTAG, T.; Cadena, E.; Valotteau, C.; Birnbaum, S. K.; Sundaram, M. V.; PUJOL, N.

Apical extracellular matrices (aECMs) are essential for tissue integrity and function in multicellular organisms, but there is limited understanding of how such matrices are assembled and organized in the extracellular environment. The Caenorhabditis elegans cuticle, a model aECM that undergoes morphogenesis during each of the worm's four larval molts, requires periodic circumferential furrows for structural integrity and immune regulation. Here, we show that furrow collagens must be cleaved from their N-terminal transmembrane domain for secretion and depend on the mucin-like pre-cuticle protein DPY-6 for their periodic assembly. While DPY-6 is dispensable for initial embryonic furrow formation, it acts as a mold during subsequent molts, ensuring pattern replication via its C-terminal cysteine cradle domain. These results reveal a central role for a transient matrix factor in organizing a periodically structured aECM, essential for both physical protection and immune homeostasis.