C. elegans mig-6encodes papilin isoforms that affect distinct aspects of DTC migration, and interacts genetically withmig-17andcollagen IV

Abstract

The gonad arms of C. elegans hermaphrodites acquire invariant shapes by guided migrations of distal tip cells (DTCs), which occur in three phases that differ in the direction and basement membrane substrata used for movement. We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette, lagrin repeats and C-terminal Kunitz-type serine proteinase inhibitory domains. We show that mutations affecting MIG-6L specifically and cell-autonomously decrease the rate of postembryonic DTC migration, mimicking a post-embryonic collagen IV deficit. We also show that MIG-6S has two separable functionsone in embryogenesis and one in the second phase of DTC migration. Genetic data suggest that MIG-6S functions in the same pathway as the MIG-17/ADAMTS metalloproteinase for guiding phase 2 DTC migrations, and MIG-17 is abnormally localized in mig-6 class-s mutants. Genetic data also suggest that MIG-6S and non-fibrillar network collagen IV play antagonistic roles to ensure normal phase 2 DTC guidance.

Tissue Architecture in the Caenorhabditis elegans Gonad Depends on Interactions Among Fibulin-1, Type IV Collagen and the ADAMTS Extracellular Protease

“…Thus, it is possible that EMB-9 may mediate FBL-1 function to promote integrin expression and cytoskeletal rearrangement in DTCs, which are required for gonadal elongation. In support of this, RNAi knockdown of ina-1 and ts let-2 and emb-9 mutants reared at nonpermissive temperatures exhibit the short-arm gonad phenotype (Cram et al 2006;Meighan and Schwarzbauer 2007;Kawano et al 2009) similar to that observed in fbl-1(tk45) mutants.…”

“…A temperature-sensitive (ts) embryonic lethal allele of emb-9, g34 , did not exhibit gonadal elongation defects at 20°, an intermediate temperature that results in growth retardation: 50% of g34 larvae and 100% of wild-type larvae shifted from 16°to 20°at the first larval stage (L1) grew to be adults after 48 hr (n = 80). Shifting mutant L2 larvae to 25°, a restrictive temperature, resulted in severe gonadal defects (100% of both anterior and posterior gonad arms; n = 20) as reported (Kawano et al 2009). g34 could not suppress the fbl-1(tk45) mutants at 20° (Figure 2A).…”

“…Shifting mutant L2 larvae to 25°, a restrictive temperature, resulted in severe gonadal defects (100% of both anterior and posterior gonad arms; n = 20) as reported (Kawano et al 2009). g34 could not suppress the fbl-1(tk45) mutants at 20° (Figure 2A).…”

An active role for basement membrane assembly and modification in tissue sculpting

“…Recent work in C. elegans has shown that the conserved matrix component fibulin is required to preserve collagen in both the gonadal and intestinal tissues -loss of fibulin does not affect collagen function during embryogenesis or early larval development, but does result in the loss of collagen during the end of larval development (Kubota et al, 2012). This loss of collagen is thought to underlie the shortened and widened gonad seen in fibulin mutants, as this phenotype can be recapitulated by shifting a temperature-sensitive collagen mutant to the restrictive temperature following embryogenesis (Kawano et al, 2009;Kubota et al, 2012). Taken together, these data indicate that there are numerous mechanisms that have evolved to regulate collagen incorporation, function and maintenance in basement membranes.…”

‘Biogeneric’ developmental processes: drivers of major transitions in animal evolution

“…Functions of some TSR proteins include stimulation of migration; others mediate adhesion or breakdown of the ECM. Papilin and ADAMTR, two TSR proteins, have reciprocal roles in Drosophila gastrulation [66], and other members of the superfamily have complementary functions in early nematode development [67].…”