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[
Matrix Biol,
2015]
The members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of secreted proteins, MIG-17 and GON-1, play essential roles in Caenorhabditis elegans gonadogenesis. The genetic and molecular analyses of these proteinases uncovered novel molecular interactions regulating the basement membrane (BM) during the migration of the gonadal leader cells. MIG-17, which is localized to the gonadal BM recruits or activates fibulin-1 and type IV collagen, which then recruits nidogen, thereby inducing the remodeling of the BM that is required for directional control of leader cell migration. GON-1 acts antagonistically with fibulin-1 to regulate the levels of type IV collagen accumulation in the gonadal BM, which facilitates active migration of the leader cells. The cooperative action of MIG-17 and GON-1 represents an excellent model for understanding the mechanisms of organogenesis mediated by ADAMTS proteinases.
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[
Curr Biol,
2005]
Apoptotic cells are removed from tissues by uptake mechanisms that depend on the GTPase Rac (CED-10 in C. elegans), which is activated by DOCK180/CED-5 in a trimolecular complex with ELMO/CED-12 and CrkII/CED-2. A study now identifies upstream components of this pathway in both worms and mammalian cells involving yet another GTPase, RhoG/MIG-2, and its activator TRIO/UNC-73.
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Curr Opin Cell Biol,
1999]
In Caenorhabditis elegans, cell migration is guided by localized cues, including molecules such as EGL-17/FGF and UNC-6/netrin. These external cues are linked to an intracellular response to migrate, at least in part, by CED-5, a homolog of DOCK180/MBC, and MIG-2, a Rac-like GTPase. In addition, metalloproteases are required for a cell migration that controls organ shape.
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[
Trends Genet,
2000]
An ADAM is a transmembrane protein that contains a disintegrin and metalloprotease domain and, therefore, it potentially has both cell adhesion and protease activities. Currently, the ADAM gene family has 29 members, although the function of most ADAM gene products is unknown. We discuss the ADAM gene products with known functions that act in a highly diverse set of biological processes, including fertilization, neurogenesis, myogenesis, embryonic TGF-alpha release and the inflammatory response.
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[
Traffic,
2009]
There is growing awareness that endocytic trafficking plays a critical role in cell-cell communication during animal development. We are beginning to understand how endocytosis can initiate, modulate or terminate signaling. In contrast, our knowledge of the mechanisms involved in secreting signaling peptides remains more limited, particularly when it comes to secretion at the apical surface in epithelial cells. In this study, we review the mechanisms that control secretion in Caenorhabditis elegans, focusing on the role of Patched family members and the V0 complex of the vacuolar-adenosine triphosphatase (V-ATPase) in secreting Hedgehog-related peptides and of MIG-14/Wls and the retromer complex in secreting EGL-20/WNT.
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Adv Exp Med Biol,
2011]
In normal development cell fusion is essential for organ formation and sexual reproduction. The nematode Caenorhabditis elegans has become an excellent system to study the mechanisms and developmental functions of cell-to-cell fusion. In this review we focus on the heterochronic regulation of cell fusion. Heterochronic genes control the timing of specific developmental events in C. elegans. The first microRNAs discovered were found as mutations that affect heterochronic development and cell-cell fusions. In addition numerous heterochronic transcription factors also control specific cell fusion events in C. elegans. We describe what is known about the heterochronic regulation of cell fusion of the epidermal seam cells. The fusogen AFF-1 was previously shown to mediate the fusion of the lateral epidermal seam cells. Here we provide evidence supporting the model in which LIN-29, the heterochronic Zinc-finger transcription factor that controls the terminal fusion of the seam cells, stimulates AFF-1 expression in the seam cells before they fuse. Therefore, the heterochronic gene LIN-29 controls AFF-1-mediated cell-cell fusion as part of the terminal differentiation program of the epidermal seam cells.
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[
Bioessays,
2007]
In C. elegans and D. melanogaster, specialized sites have an important role in meiotic recombination. Recent evidence has shown that these sites in C. elegans have a role in synapsis. Here we compare the initiation of synapsis in organisms with specialized sites and those without. We propose that, early in prophase, synapsis requires an initiator to overcome inhibitory factors that function to prevent synaptonemal complex (SC) formation between nonhomologous sequences. These initiators of SC formation can be stimulated by crossover sites, possibly other types of recombination sites and also specialized sites where recombination does not occur. BioEssays 29: 217-226, 2007. (c) 2007 Wiley Periodicals, Inc.
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Curr Opin Genet Dev,
2008]
The simplicity of C. elegans makes it an outstanding system to study the role of Wnt signaling in the development. Many asymmetric cell divisions in C. elegans require the Wnt/beta-catenin asymmetry pathway. Recent studies confirm that SYS-1 is a structurally and functionally divergent beta-catenin, and implicate lipids and retrograde trafficking in maintenance of WRM-1/beta-catenin asymmetry. Wnts also regulate short-range events such as spindle rotation and gastrulation, and a PCP-like pathway regulates asymmetric divisions. Long-range, cell non-autonomous Wnt signals regulate vulval induction. Both short-range and long-range Wnt signalings are regulated by recycling of MIG-14/Wntless via the retromer complex. These studies indicate that C. elegans continues to be useful for identifying new, conserved mechanisms underlying Wnt signaling in metazoans.
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[
Trends Cell Biol,
2008]
A network of connections is established as neural circuits form between neurons. To make these connections, neurons initiate asymmetric axon outgrowth in response to extracellular guidance cues. Within the specialized growth cones of migrating axons, F-actin and microtubules asymmetrically accumulate where an axon projects forward. Although many guidance cues, receptors and intracellular signaling components that are required for axon guidance have been identified, the means by which the asymmetry is established and maintained is unclear. Here, we discuss recent studies in invertebrate and vertebrate organisms that define a signaling module comprising UNC-6 (the Caenorhabditis elegans ortholog of netrin), UNC-40 (the C. elegans ortholog of DCC), PI3K, Rac and MIG-10 (the C. elegans ortholog of lamellipodin) and we consider how this module could establish polarized outgrowth in response to guidance cues.
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[
Biol Chem,
2006]
The conserved oligomeric Golgi (COG) complex is an octameric protein complex associated with the Golgi apparatus and is required for proper sorting and glycosylation of Golgi resident enzymes and secreted proteins. Although COG complex function has been extensively studied at the cellular and subcellular levels, its role in animal development mostly remains unknown. Recently, mutations in the components of the COG complex were found to cause abnormal gonad morphogenesis in Caenorhabditis elegans. In C. elegans, the COG complex acts in the glycosylation of an ADAM (a disintegrin and metalloprotease) family protein, MIG-17, which directs migration of gonadal distal tip cells to lead gonad morphogenesis. This is the first link between the COG complex and the function of an ADAM protease that is directly involved in organ morphogenesis, demonstrating the potential of C. elegans as a model system to study COG function in animal development.