C. elegans Apical Extracellular Matrices Shape Epithelia

Abstract

Apical extracellular matrices (aECMs) coat exposed surfaces of epithelia to shape developing tissues and protect them from environmental insults. Despite their widespread importance for human health, aECMs are poorly understood compared to basal and stromal ECMs. The nematode Caenorhabditis elegans contains a variety of distinct aECMs, some of which share many of the same types of components (lipids, lipoproteins, collagens, zona pellucida domain proteins, chondroitin glycosaminoglycans and proteoglycans) with mammalian aECMs. These aECMs include the eggshell, a glycocalyx-like pre-cuticle, both collagenous and chitin-based cuticles, and other understudied aECMs of internal epithelia. C. elegans allows rapid genetic manipulations and live imaging of fluorescently-tagged aECM components, and is therefore providing new insights into aECM structure, trafficking, assembly, and functions in tissue shaping.

Form and function of the apical extracellular matrix: new insights from Caenorhabditis elegans, Drosophila melanogaster, and the vertebrate inner ear

“…The C. elegans epidermis (known as the hypodermis) secretes a complex multilayered aECM beginning in late embryogenesis and thereafter in four molts, resulting in the mature adult cuticle consisting of an outer surface coat, a lipid-rich epicuticle, and the multilayered collagenous cuticle ( Figure 1a ) 6 – 8 . Other epithelial aECMs in C. elegans include those of internal tubes, such as the excretory duct and vulva, and specialized aECMs of sensory organs 4 , 9 . Recent bioinformatic analysis has enumerated components of the C. elegans ECM (including aECMs), predicting a total “matrisome” of over 700 proteins 10 .…”

“…External aECMs can incorporate lipid layers that provide desiccation resistance and permeability barrier function. Internal aECMs, such as those of tubular epithelia, often have transient developmental roles in shaping tube morphology 3 , 4 . Other aECMs found in vertebrates include the vascular glycocalyx, the mucin-rich coating of the gastrointestinal tract and upper airways, and the alveolar surfactant of lungs.…”

TheC. elegansPTCHD homolog PTR-4 is required for proper organization of the pre-cuticular apical extracellular matrix

“…Previous studies showed that RNAi-mediated knockdown of many C. elegans ptr genes led to defects in cuticular structure and molting (Hao et al, 2006a; Zugasti et al, 2005), suggesting a potential role for PTR proteins in trafficking or export of components of the apical extracellular matrix (aECM). C. elegans has multiple distinct types of aECM, including a chitinous eggshell and a collagenous cuticle that must be disassembled and rebuilt during each of four larval molts (Cohen and Sundaram, 2020; Page and Johnstone, 2007; Stein and Golden, 2018). Prior to the generation of each new cuticle, a molecularly distinct aECM, termed the sheath or pre-cuticle, coats external epithelia (Cohen et al, 2020b; Cohen and Sundaram, 2020; Priess and Hirsh, 1986; Vuong-Brender et al, 2017).…”

“…C. elegans has multiple distinct types of aECM, including a chitinous eggshell and a collagenous cuticle that must be disassembled and rebuilt during each of four larval molts (Cohen and Sundaram, 2020; Page and Johnstone, 2007; Stein and Golden, 2018). Prior to the generation of each new cuticle, a molecularly distinct aECM, termed the sheath or pre-cuticle, coats external epithelia (Cohen et al, 2020b; Cohen and Sundaram, 2020; Priess and Hirsh, 1986; Vuong-Brender et al, 2017). Similar to some mammalian aECMs such as lung surfactant (Pérez-Gil, 2008) or eye tear film (Dartt, 2011), all of these C. elegans aECMs appear to contain layers with significant lipid content (Bai et al, 2020; Blaxter, 1993; Dartt, 2011; Forman-Rubinsky et al, 2017; Pu et al, 2017; Schultz and Gumienny, 2012).…”

“…The pre-cuticle is a transient aECM that contains multiple proteins of the Zona Pellucida (ZP) domain, extracellular leucine-rich repeat only (eLRRon), and lipocalin (putative lipid transporter) families (Cohen et al, 2019; Cohen et al, 2020b; Forman-Rubinsky et al, 2017; Gill et al, 2016; Katz et al, 2018; Kelley et al, 2015; Mancuso et al, 2012; Vuong-Brender et al, 2017). It is present in the developing embryo and prior to each larval molt, and it shapes multiple epithelial tissues and helps pattern the subsequent collagenous cuticle (Cohen and Sundaram, 2020). We show that ptr-4 mutants share many phenotypes with pre-cuticle mutants, including defects in eggshell dissolution, tube shaping, alae (cuticle ridge) structure, and cuticle barrier function.…”