Cell migration in invertebrates: clues from border and distal tip cells

AbstractThe 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 inCaenorhabditis elegans. InC. 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 ofC. elegansas a model system to study COG function in animal development.

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

PLoS ONE ◽

10.1371/journal.pone.0240571 ◽

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.

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Mutations Affecting Symmetrical Migration of Distal Tip Cells in Caenorhabditis elegans

Genetics ◽

10.1093/genetics/152.3.985 ◽

1999 ◽

Vol 152 (3) ◽

pp. 985-997 ◽

Cited By ~ 2

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.

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

Development ◽

10.1242/dev.127.3.585 ◽

2000 ◽

Vol 127 (3) ◽

pp. 585-594 ◽

Cited By ~ 4

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.

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

Development ◽

10.1242/dev.125.16.3213 ◽

1998 ◽

Vol 125 (16) ◽

pp. 3213-3224 ◽

Cited By ~ 2

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.

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

Developmental Biology ◽

10.1016/j.ydbio.2014.10.008 ◽

2015 ◽

Vol 397 (2) ◽

pp. 151-161 ◽

Cited By ~ 3

Author(s):

Tetsuhiro Kikuchi ◽

Yukimasa Shibata ◽

Hon-Song Kim ◽

Yukihiko Kubota ◽

Sawako Yoshina ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Distal Tip Cells ◽

Domain Protein ◽

Tip Cells

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C. elegans Agrin Is Expressed in Pharynx, IL1 Neurons and Distal Tip Cells and Does Not Genetically Interact with Genes Involved in Synaptogenesis or Muscle Function

PLoS ONE ◽

10.1371/journal.pone.0000731 ◽

2007 ◽

Vol 2 (8) ◽

pp. e731 ◽

Cited By ~ 16

Author(s):

Ana Hrus ◽

Gordon Lau ◽

Harald Hutter ◽

Susanne Schenk ◽

Jacqueline Ferralli ◽

...

Keyword(s):

Muscle Function ◽

C Elegans ◽

Distal Tip Cells ◽

Tip Cells

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Multiple Signaling Mechanisms of the UNC-6/netrin Receptors UNC-5 and UNC-40/DCC in Vivo

Genetics ◽

10.1093/genetics/158.3.1071 ◽

2001 ◽

Vol 158 (3) ◽

pp. 1071-1080 ◽

Cited By ~ 1

Author(s):

David C Merz ◽

Hong Zheng ◽

Marie T Killeen ◽

Aldis Krizus ◽

Joseph G Culotti

Keyword(s):

Dominant Negative ◽

Genetic Interactions ◽

Receptor Subtypes ◽

Negative Effects ◽

Receptor Complexes ◽

Guidance Cue ◽

Distal Tip Cells ◽

Multiple Signaling ◽

Tip Cells

Abstract Cell and growth cone migrations along the dorsoventral axis of Caenorhabditis elegans are mediated by the UNC-5 and UNC-40 receptor subtypes for the secreted UNC-6 guidance cue. To characterize UNC-6 receptor function in vivo, we have examined genetic interactions between unc-5 and unc-40 in the migrations of the hermaphrodite distal tip cells. We report that cell migration defects as severe as those associated with a null mutation in unc-6 are produced only by null mutations in both unc-5 and unc-40, indicating that either receptor retains some partial function in the absence of the other. We show that hypomorphic unc-5 alleles exhibit two distinct types of interallelic genetic interactions. In an unc-40 wild-type genetic background, some pairs of hypomorphic unc-5 alleles exhibit a partial allelic complementation. In an unc-40 null background, however, we observed that unc-5 hypomorphs exhibit dominant negative effects. We propose that the UNC-5 and UNC-40 netrin receptors can function to mediate chemorepulsion in DTC migrations either independently or together, and the observed genetic interactions suggest that this flexibility in modes of signaling results from the formation of a variety of oligomeric receptor complexes.

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