scholarly journals Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans

2020 ◽  
Author(s):  
Ayaka Imanishi ◽  
Yuma Aoki ◽  
Masaki Kakehi ◽  
Shunsuke Mori ◽  
Tomomi Takano ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Basement Membrane ◽  
Collagen Iv ◽  
Wild Type ◽  
Suppressor Mutations ◽  
Genetic Suppressors ◽  
Basement Membrane Protein ◽  
Distal Tip Cells ◽  
Tip Cells ◽  
Shaped Pattern

AbstractDuring development of the Caenorhabditis elegans gonad, the gonadal leader cells, called distal tip cells (DTCs), migrate in a U-shaped pattern to form the U-shaped gonad arms. The ADAMTS (adisintegrin and metalloprotease with thrombospondin motifs) family metalloproteases MIG-17 and GON-1 are required for correct DTC migration. Mutations in mig-17 result in misshapen gonads due to the misdirected DTC migration, and mutations in gon-1 result in shortened and swollen gonads due to the premature termination of DTC migration. Although the phenotypes shown by mig-17 and gon-1 mutants are very different from one another, mutations that result in amino acid substitutions in the same basement membrane protein genes, emb-9/collagen IV a1, let-2/collagen IV a2 and fbl-1/fibulin-1, were identified as genetic suppressors of mig-17 and gon-1 mutants. To understand the roles shared by these two proteases, we examined the effects of the mig-17 suppressors on gon-1 and the effects of the gon-1 suppressors and enhancers on mig-17 gonadal defects. Some of the emb-9, let-2 and fbl-1 mutations suppressed both mig-17 and gon-1, whereas others acted only on mig-17 or gon-1. These results suggest that mig-17 and gon-1 have their specific functions as well as functions commonly shared between them for gonad formation. The levels of collagen IV accumulation in the DTC basement membrane were significantly higher in the gon-1 mutants as compared with wild type and were reduced to the wild-type levels when combined with suppressor mutations, but not with enhancer mutations, suggesting that the ability to reduce collagen IV levels is important for gon-1 suppression.

scholarly journals Genetic interactions among ADAMTS metalloproteases and basement membrane molecules in cell migration in Caenorhabditis elegans

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0240571
Author(s):  
Ayaka Imanishi ◽  
Yuma Aoki ◽  
Masaki Kakehi ◽  
Shunsuke Mori ◽  
Tomomi Takano ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Basement Membrane ◽  
Collagen Iv ◽  
Wild Type ◽  
Suppressor Mutations ◽  
Genetic Suppressors ◽  
Basement Membrane Protein ◽  
Distal Tip Cells ◽  
Tip Cells ◽  
Shaped Pattern

During development of the Caenorhabditis elegans gonad, the gonadal leader cells, called distal tip cells (DTCs), migrate in a U-shaped pattern to form the U-shaped gonad arms. The ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family metalloproteases MIG-17 and GON-1 are required for correct DTC migration. Mutations in mig-17 result in misshapen gonads due to the misdirected DTC migration, and mutations in gon-1 result in shortened and swollen gonads due to the premature termination of DTC migration. Although the phenotypes shown by mig-17 and gon-1 mutants are very different from one another, mutations that result in amino acid substitutions in the same basement membrane protein genes, emb-9/collagen IV a1, let-2/collagen IV a2 and fbl-1/fibulin-1, were identified as genetic suppressors of mig-17 and gon-1 mutants. To understand the roles shared by these two proteases, we examined the effects of the mig-17 suppressors on gon-1 and the effects of the gon-1 suppressors and enhancers on mig-17 gonadal defects. Some of the emb-9, let-2 and fbl-1 mutations suppressed both mig-17 and gon-1, whereas others acted only on mig-17 or gon-1. These results suggest that mig-17 and gon-1 have their specific functions as well as functions commonly shared between them for gonad formation. The levels of collagen IV accumulation in the DTC basement membrane were significantly higher in the gon-1 mutants as compared with wild type and were reduced to the wild-type levels when combined with suppressor mutations, but not with enhancer mutations, suggesting that the ability to reduce collagen IV levels is important for gon-1 suppression.

scholarly journals Peroxidasin-mediated bromine enrichment of basement membranes

2020 ◽  
Vol 117 (27) ◽  
pp. 15827-15836
Author(s):  
Cuiwen He ◽  
Wenxin Song ◽  
Thomas A. Weston ◽  
Caitlyn Tran ◽  
Ira Kurtz ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Knockout Mice ◽  
Structural Integrity ◽  
Secondary Ion Mass Spectrometry ◽  
Human Kidney ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Basement Membrane Protein ◽  
Mammalian Tissues ◽  
Cross Links

Bromine and peroxidasin (an extracellular peroxidase) are essential for generating sulfilimine cross-links between a methionine and a hydroxylysine within collagen IV, a basement membrane protein. The sulfilimine cross-links increase the structural integrity of basement membranes. The formation of sulfilimine cross-links depends on the ability of peroxidasin to use bromide and hydrogen peroxide substrates to produce hypobromous acid (HOBr). Once a sulfilimine cross-link is created, bromide is released into the extracellular space and becomes available for reutilization. Whether the HOBr generated by peroxidasin is used very selectively for creating sulfilimine cross-links or whether it also causes oxidative damage to bystander molecules (e.g., generating bromotyrosine residues in basement membrane proteins) is unclear. To examine this issue, we used nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to define the distribution of bromine in mammalian tissues. We observed striking enrichment of bromine (79Br,81Br) in basement membranes of normal human and mouse kidneys. In peroxidasin knockout mice, bromine enrichment of basement membranes of kidneys was reduced by ∼85%. Proteomic studies revealed bromination of tyrosine-1485 in the NC1 domain of α2 collagen IV from kidneys of wild-type mice; the same tyrosine was brominated in collagen IV from human kidney. Bromination of tyrosine-1485 was reduced by >90% in kidneys of peroxidasin knockout mice. Thus, in addition to promoting sulfilimine cross-links in collagen IV, peroxidasin can also brominate a bystander tyrosine. Also, the fact that bromine enrichment is largely confined to basement membranes implies that peroxidasin activity is largely restricted to basement membranes in mammalian tissues.

Mutations Affecting Symmetrical Migration of Distal Tip Cells in Caenorhabditis elegans

Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 985-997 ◽  
Author(s):  
Kiyoji Nishiwaki
Keyword(s):  
Caenorhabditis Elegans ◽  
Rotational Symmetry ◽  
The Other ◽  
Body Region ◽  
Distal Tip Cells ◽  
Complementation Groups ◽  
Mutant Phenotypes ◽  
Tip Cells ◽  
Posterior Body Region ◽  
Null Mutants

Abstract The rotational symmetry of the Caenorhabditis elegans gonad arms is generated by the symmetrical migration of two distal tip cells (DTCs), located on the anterior and posterior ends of the gonad primordium. Mutations that cause asymmetrical migration of the two DTCs were isolated. All seven mutations were recessive and assigned to six different complementation groups. vab-3(k121) and vab-3(k143) affected anterior DTC migration more frequently than posterior, although null mutants showed no bias. The other five mutations, mig-14(k124), mig-17(k113), mig-18(k140), mig-19(k142), and mig-20(k148), affected posterior DTC migration more frequently than anterior. These observations imply that the migration of each DTC is regulated differently. mig-14 and mig-19 also affected the migration of other cells in the posterior body region. Four distinct types of DTC migration abnormalities were defined on the basis of the mutant phenotypes. vab-3; mig-14 double mutants exhibited the types of DTC migration defects seen for vab-3 single mutants. Combination of mig-17 and mig-18 or mig-19, which are characterized by the same types of posterior DTC migration defects, exhibited strong enhancement of anterior DTC migration defects, suggesting that they affect the same or parallel pathways regulating anterior DTC migration.

Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans

Development ◽  
2000 ◽  
Vol 127 (3) ◽  
pp. 585-594 ◽  
Author(s):  
M. Su ◽  
D.C. Merz ◽  
M.T. Killeen ◽  
Y. Zhou ◽  
H. Zheng ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Developmental Stage ◽  
Phase 1 ◽  
Critical Role ◽  
The Body ◽  
Dependent Manner ◽  
C Elegans ◽  
Guidance Cue ◽  
Distal Tip Cells ◽  
Tip Cells

Cell migrations play a critical role in animal development and organogenesis. Here, we describe a mechanism by which the migration behaviour of a particular cell type is regulated temporally and coordinated with over-all development of the organism. The hermaphrodite distal tip cells (DTCs) of Caenorhabditis elegans migrate along the body wall in three sequential phases distinguished by the orientation of their movements, which alternate between the anteroposterior and dorsoventral axes. The ventral-to-dorsal second migration phase requires the UNC-6 netrin guidance cue and its receptors UNC-5 and UNC-40, as well as additional, UNC-6-independent guidance systems. We provide evidence that the transcriptional upregulation of unc-5 in the DTCs is coincident with the initiation of the second migration phase, and that premature UNC-5 expression in these cells induces precocious turning in an UNC-6-dependent manner. The DAF-12 steroid hormone receptor, which regulates developmental stage transitions in C. elegans, is required for initiating the first DTC turn and for coincident unc-5 upregulation. We also present evidence for the existence of a mechanism that opposes or inhibits UNC-5 function during the longitudinal first migration phase and for a mechanism that facilitates UNC-5 function during turning. The facilitating mechanism presumably does not involve transcriptional regulation of unc-5 but may represent an inhibition of the phase 1 mechanism that opposes or inhibits UNC-5. These results, therefore, reveal the existence of two mechanisms that regulate the UNC-5 receptor that are critical for responsiveness to the UNC-6 netrin guidance cue and for linking the directional guidance of migrating distal tip cells to developmental stage advancements.

A tissue-specific knock-out strategy reveals that lin-26 is required for the formation of the somatic gonad epithelium in Caenorhabditis elegans

Development ◽  
1998 ◽  
Vol 125 (16) ◽  
pp. 3213-3224 ◽  
Author(s):  
B.G. den Boer ◽  
S. Sookhareea ◽  
P. Dufourcq ◽  
M. Labouesse
Keyword(s):  
Caenorhabditis Elegans ◽  
Null Mutant ◽  
Similar Function ◽  
Knock Out ◽  
Somatic Gonad ◽  
Distal Tip Cells ◽  
Germline Proliferation ◽  
Tip Cells ◽  
New Alleles ◽  
Lineage Analysis

The Caenorhabditis elegans LIN-26 protein is required to specify and/or maintain the fates of all non-neuronal ectodermal cells. Here we show that lin-26 is expressed until the somatic gonad primordium stage in all cells of the somatic gonad, except in distal tip cells, and later in all uterine cells. To determine if lin-26 functions in the somatic gonad, we have generated gonad-specific lin-26 alleles obtained by integration of lin-26 promoter deletion derivatives into a lin-26 null mutant background. In this way, we rescued the lethal phenotype imparted by lin-26 null mutations and uncovered a highly penetrant sterile phenotype. Specifically, the strongest of these new alleles was characterized by the absence of lin-26 expression in the somatic gonad, the presence of endomitotic oocytes, decreased germline proliferation, a protruding vulva and a less penetrant absence of gonad arms. Lineage analysis of mutant somatic gonads and examination of several markers expressed in the spermatheca, sheath cells, distal tip cells and the uterus, suggest that LIN-26 is required in sheath, spermatheca and uterine precursors, and in uterine cells. We conclude that lin-26 performs a similar function in the non-neuronal ectoderm and the somatic gonad, a mesoderm derivative, and we speculate that lin-26 is required to express epithelial characteristics.

scholarly journals The BED finger domain protein MIG-39 halts migration of distal tip cells in Caenorhabditis elegans

2015 ◽  
Vol 397 (2) ◽  
pp. 151-161 ◽  
Author(s):  
Tetsuhiro Kikuchi ◽  
Yukimasa Shibata ◽  
Hon-Song Kim ◽  
Yukihiko Kubota ◽  
Sawako Yoshina ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Distal Tip Cells ◽  
Domain Protein ◽  
Tip Cells

scholarly journals Genetic interaction between Caenorhabditis elegans teneurin ten-1 and prolyl 4-hydroxylase phy-1 and their function in collagen IV–mediated basement membrane integrity during late elongation of the embryo

2011 ◽  
Vol 22 (18) ◽  
pp. 3331-3343 ◽  
Author(s):  
Ulrike Topf ◽  
Ruth Chiquet-Ehrismann
Keyword(s):  
Caenorhabditis Elegans ◽  
Basement Membrane ◽  
Body Wall ◽  
Catalytic Domain ◽  
Genetic Interaction ◽  
Membrane Integrity ◽  
Collagen Iv ◽  
Basement Membranes ◽  
A Genome ◽  
Body Wall Muscles

Teneurins are a family of phylogenetically conserved proteins implicated in pattern formation and morphogenesis. The sole orthologue in Caenorhabditis elegans, ten-1, is important for hypodermal cell migration, neuronal migration, path finding and fasciculation, gonad development, and basement membrane integrity of some tissues. However, the mechanisms of TEN-1 action remain to be elucidated. Using a genome-wide RNA interference approach, we identified phy-1 as a novel interaction partner of ten-1. phy-1 codes for the catalytic domain of collagen prolyl 4-hydroxylase. Loss of phy-1 significantly enhanced the embryonic lethality of ten-1 null mutants. Double-mutant embryos arrested during late elongation with epidermal defects, disruption of basement membranes, and detachment of body wall muscles. We found that deletion of phy-1 caused aggregation of collagen IV in body wall muscles in elongated embryos and triggered the loss of tissue integrity in ten-1 mutants. In addition, phy-1 and ten-1 each genetically interact with genes encoding collagen IV. These findings support a functional mechanism in which loss of ten-1, together with a reduction of assembled and secreted basement membrane collagen IV protein, leads to detachment of the epidermis from muscle cells during late elongation of the embryo when mechanical stress is generated by muscle contractions.

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