Genetics of Extracellular Matrix Remodeling During Organ Growth Using the Caenorhabditis elegans Pharynx Model

Abstract

The organs of animal embryos are typically covered with an extracellular matrix (ECM) that must be carefully remodeled as these organs enlarge during post-embryonic growth; otherwise, their shape and functions may be compromised. We previously described the twisting of the Caenorhabditis elegans pharynx (here called the Twp phenotype) as a quantitative mutant phenotype that worsens as that organ enlarges during growth. Mutations previously known to cause pharyngeal twist affect membrane proteins with large extracellular domains (DIG-1 and SAX-7), as well as a C. elegans septin (UNC-61). Here we show that two novel alleles of the C. elegans papilin gene, mig-6(et4) and mig-6(sa580), can also cause the Twp phenotype. We also show that overexpression of the ADAMTS protease gene mig-17 can suppress the pharyngeal twist in mig-6 mutants and identify several alleles of other ECM-related genes that can cause or influence the Twp phenotype, including alleles of fibulin (fbl-1), perlecan (unc-52), collagens (cle-1, dpy-7), laminins (lam-1, lam-3), one ADAM protease (sup-17), and one ADAMTS protease (adt-1). The Twp phenotype in C. elegans is easily monitored using light microscopy, is quantitative via measurements of the torsion angle, and reveals that ECM components, metalloproteinases, and ECM attachment molecules are important for this organ to retain its correct shape during post-embryonic growth. The Twp phenotype is therefore a promising experimental system to study ECM remodeling and diseases.

Multiple Phenotypes Resulting from a Mutagenesis Screen for Pharynx Muscle Mutations in Caenorhabditis elegans

“…Within the region of PAS136 mapping, there are 322 genes; 39 were chosen for screening using recorded L1 arrest as a necessary parameter; experiments showing pharynx phenotypes are listed (Table 4). A partially penetrant phenotype similar to that of PAS136 resulted from lam-3 (T22A3.8) RNAi and blmp-1 (F25D7.3) RNAi (Figure 3C and D); the laminin gene lam-3 has previously been shown to affect the extracellular matrix and pharynx cohesion, while blmp-1 is described as a homolog of the B lymphocyte-induced maturation protein 1 on WormBase [24], [25]. Other pharyngeal phenotypes were observed that did not mimic PAS136, such as the Pun phenotypes of mom-5 (T23F8.1) and hmr-1 (W02B9.1) (data not shown and Figure 3E).…”

The Adhesion Molecule KAL-1/anosmin-1 Regulates Neurite Branching through a SAX-7/L1CAM–EGL-15/FGFR Receptor Complex

“…In addition to non-neuronal functions (Grana et al, 2010; Jafari et al, 2010; Lynch et al, 2012), sax-7 /L1CAM is important for development and maintenance of different aspects of the nervous system (Sasakura et al, 2005; Wang et al, 2005; Pocock et al, 2008; Dong et al, 2013; Salzberg et al, 2013; Opperman et al, 2015). Interestingly, distinct domains of the protein are necessary for different processes.…”

Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders

“…It is unclear what drives this effect on sheath cell integrity, but it has been speculated that it is mediated by a loss of adhesion signals to the cells from the Unc-52-depleted basement membrane. Unc-52 mutation or depletion has been tied to developmental defects in the pharynx (Jafari et al, 2010; Morck et al, 2010). …”