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Pre-cuticle DPY 6 acts as a blueprint for aECM periodic organization in C. elegans

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

2026-02-23 developmental biology
10.64898/2026.02.21.707041 bioRxiv
Show abstract

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 worms 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.

Published in PLOS Genetics (predicted rank #9) · training set

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