Multiscale patterning outside the cell: the C. elegans model extracellular matrix

The skin forms the first line of defense of an organism against external mechanical damage and pathogen intrusion. Across species, skin layers contain a complex apical extracellular matrix (aECM) composed of proteins, glycans and lipids that together maintain the permeability barrier and provide structural integrity. Aberrant skin function in humans underlies a range of pathologies ranging from chronic defects in wound repair to hypertrophic scarring and fibrosis. We use the simple skin layer of the nematode C elegans as a tractable model for how aECM is generated and patterned in vivo. The skin’s apical ECM or cuticle is composed of dozens of collagens and non-collagenous proteins. Three collagens collaborate to form intricately patterned columns or ‘struts’ that hold the cortical and basal matrix layers apart in the adult, and which function in damage or mechanical sensation (Adams, Pooranachithra et al 2023 Nat Comms). The cortical layer of the aECM contains diverse non-collagenous proteins. Among these, the epicuticlins are defined by perfect or near-perfect low-complexity tandem repeats and play specific roles in maintenance of the lipid layers of the matrix (Pooranachithra et al 2024 Development). The aECM contains many other substructures and compartments whose patterning and molecular organization remain little-understood. To better understand multiscale aECM patterning we have developed a toolkit of over 100 strains expressing endogenously labeled matrix components (in collaboration with Jordan Ward, UC Santa Cruz). Localization patterns of such knockin strains reveal multiple previously unknown matrix compartments. Understanding the patterning of this model aECM should help understand patterning and function of complex aECMs such as the vertebrate skin.