Tissue Architecture in the C. elegans Gonad Depends on Interactions among Fibulin-1, Type IV collagen and the ADAMTS Extracellular Protease
نویسندگان
چکیده
Molecules in the extracellular matrix (ECM) regulate cellular behavior in both development and pathology. Fibulin-1 is a conserved ECM protein. The Caenorhabditis elegans ortholog, FBL-1, regulates gonad-arm elongation and expansion by acting antagonistically to GON-1, an ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family protease. The elongation of gonad arms is directed by gonadal distal tip cells (DTCs). Here we report that a dominant mutation in the EMB-9/type IV collagen α1 subunit can compensate for loss of FBL-1 activity in gonadogenesis. A specific amino acid substitution in the NC1 domain of EMB-9 suppressed the fbl-1 null mutant. FBL-1 was required to maintain wild-type EMB-9 in the basement membrane (BM), whereas mutant EMB-9 was retained in the absence of FBL-1. EMB-9 (either wild type or mutant) localization in the BM enhanced PAT-3/β-integrin expression in DTCs. In addition, overexpression of PAT-3 partially rescued the DTC migration defects in fbl-1 mutants, suggesting that EMB-9 acts in part through PAT-3 to control DTC migration. In contrast to the suppression of fbl-1(tk45), mutant EMB-9 enhanced the gonadal defects of gon-1(e1254), suggesting that it gained a function similar to that of wild-type FBL-1, which promotes DTC migration by inhibiting GON-
منابع مشابه
Organ Length Control by an ADAMTS Extracellular Protease in Caenorhabditis elegans.
MIG-17, a secreted protease of the ADAMTS family, acts in the directed migration of gonadal distal tip cells (DTCs) through regulation of the gonadal basement membrane in Caenorhabditis elegans Here, we show that MIG-17 is also required for the control of pharynx elongation during animal growth. We found that the pharynx was elongated in mig-17 mutants compared with wild type. MIG-17 localized ...
متن کاملGON-1 and Fibulin Have Antagonistic Roles in Control of Organ Shape
Most developing organs are surrounded by an extracellular matrix (ECM), which must be remodeled to accommodate growth and morphogenesis. In C. elegans, the GON-1 ADAMTS metalloprotease regulates both elongation and shape of the developing gonad . Here, we report that either human ADAMTS-4 or ADAMTS-9 can substitute for GON-1 in transgenic worms, suggesting functional conservation between human ...
متن کاملRegulation of synaptic extracellular matrix composition is critical for proper synapse morphology.
Synapses are surrounded by a layer of extracellular matrix (ECM), which is instrumental for their development and maintenance. ECM composition is dynamically controlled by proteases, but how the precise composition of the ECM affects synaptic morphology is largely unknown. Through an unbiased forward genetic screen, we found that Caenorhabditis elegans gon-1, a conserved extracellular ADAMTS pr...
متن کاملBasement membranes.
Basement membranes are thin, specialized extracellular matrices surrounding most tissues in all metazoans. The compositions and functions of basement membranes have generally been well conserved throughout the subkingdom. Genetic analyses of basement membrane components in C. elegans have provided insights into their assembly and functions during development. Immuno- or GFP-tagged localization ...
متن کاملGenetics of extracellular matrix remodeling during organ growth using the Caenorhabditis elegans pharynx model.
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 orga...
متن کامل