Strategies for control of pattern formation in
            Caenorhabditis elegans

In this paper, strategies for controlling pattern formation in Caenorhabditis elegans are reviewed. The somatic tissues of this small nematode develop, in large part, by invariant cell lineages, whereas the germ-line tissue arises primarily by a variable pattern of divisions. The spatial organization of the germ-line tissue depends on special regulatory cells, the distal tip cells, which appear to influence nearby germ cells to remain in mitosis. In somatic tissues, the problem of specifying that a cell in a particular position assumes a particular fate seems to be controlled by a number of different strategies. These include the production of non-equivalent cells in particular positions of the lineage tree, local interactions between apparently equivalent cells in close contact, and the influence of another special regulatory cell, the anchor cell, over certain neighbouring cells.

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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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Capillarity and active cell movement at mesendoderm translocation in the Xenopus gastrula

Development ◽

10.1242/dev.198960 ◽

2021 ◽

pp. dev.198960

Author(s):

Martina Nagel ◽

Debanjan Barua ◽

Erich W. Damm ◽

Jubin Kashef ◽

Ralf Hofmann ◽

...

Keyword(s):

Close Contact ◽

Cell Mass ◽

Cell Movement ◽

Leading Edge ◽

Active Cell ◽

Similar Process ◽

A Cell ◽

Tissue Surface Tension ◽

Tip Cells ◽

Vertical Shearing

During Xenopus gastrulation, leading edge mesendoderm (LEM) advances animally as wedge-shaped cell mass over the vegetally moving blastocoel roof (BCR). We show that close contact across the BCR-LEM interface correlates with attenuated net advance of the LEM, which is therefore pulled forward by tip cells while the remaining LEM frequently separates from the BCR. Nevertheless, lamellipodia persist on the detached LEM surface. They attach to adjacent LEM cells and depend on PDGF-A, cell surface fibronectin and cadherin. We argue that active cell motility on the LEM surface prevents adverse capillary effects in the liquid LEM tissue as it moves by being pulled. It counters tissue surface tension effects with oriented cell movement and bulges the LEM surface out to keep it close to the curved BCR without attaching to it. Proximity to the BCR is necessary in turn for the maintenance and orientation of lamellipodia that permit mass cell movement with minimal substratum contact. Together with a similar process in epithelial invagination, vertical telescoping, the cell movement at the LEM surface defines a novel type of cell rearrangement, vertical shearing.

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The PAF1 complex cell-autonomously promotes oogenesis in Caenorhabditis elegans

10.1101/2021.08.18.456829 ◽

2021 ◽

Author(s):

Yukihiko Kubota ◽

Natsumi Ota ◽

Hisashi Takatsuka ◽

Takuma Unno ◽

Shuichi Onami ◽

...

Keyword(s):

Caenorhabditis Elegans ◽

Rna Polymerase Ii ◽

Oocyte Maturation ◽

Germ Line ◽

Biological Processes ◽

Wild Type ◽

Expression Of Genes ◽

A Cell ◽

Precise Role

The RNA polymerase II-associated factor 1 complex (PAF1C) is a protein complex that consists of LEO1, RTF1, PAF1, CDC73, and CTR9, and has been shown to be involved in Pol II-mediated transcriptional and chromatin regulation. Although it has been shown to regulate a variety of biological processes, the precise role of the PAF1C during germ line development has not been clarified. In this study, we found that reduction in the function of the PAF1C components, LEO-1, RTFO-1, PAFO-1, CDC-73, and CTR-9, in Caenorhabditis elegans affects cell volume expansion of oocytes. Defects in oogenesis were also confirmed using an oocyte maturation marker, OMA-1::GFP. While four to five OMA-1::GFP-positive oocytes were observed in wild-type animals, their numbers were significantly decreased in pafo-1 mutantand leo-1(RNAi), cdc-73(RNAi), and pafo-1(RNAi) animals. Expression of a functional PAFO-1::mCherry transgene in the germline significantly rescued the oogenesis-defective phenotype of the pafo-1 mutants, suggesting that expression of the PAF1C in germ cells is required for oogenesis. Notably, overexpression of OMA-1::GFP partially rescued the oogenesis defect in the pafo-1 mutants. Based on our findings, we propose that the PAF1C promotes oogenesis in a cell-autonomous manner by positively regulating the expression of genes involved in oocyte maturation.

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fog-1, a regulatory gene required for specification of spermatogenesis in the germ line of Caenorhabditis elegans.

Genetics ◽

10.1093/genetics/125.1.29 ◽

1990 ◽

Vol 125 (1) ◽

pp. 29-39 ◽

Cited By ~ 8

Author(s):

M K Barton ◽

J Kimble

Keyword(s):

Caenorhabditis Elegans ◽

Germ Cell ◽

Germ Line ◽

Regulatory Gene ◽

Sensitive Period ◽

Temperature Sensitive ◽

Wild Type ◽

Male Germ Line ◽

Somatic Tissues ◽

Lines Of Evidence

Abstract In wild-type Caenorhabditis elegans, the XO male germ line makes only sperm and the XX hermaphrodite germ line makes sperm and then oocytes. In contrast, the germ line of either a male or a hermaphrodite carrying a mutation of the fog-1 (feminization of the germ line) locus is sexually transformed: cells that would normally make sperm differentiate as oocytes. However, the somatic tissues of fog-1 mutants remain unaffected. All fog-1 alleles identified confer the same phenotype. The fog-1 mutations appear to reduce fog-1 function, indicating that the wild-type fog-1 product is required for specification of a germ cell as a spermatocyte. Two lines of evidence indicate that a germ cell is determined for sex at about the same time that it enters meiosis. These include the fog-1 temperature sensitive period, which coincides in each sex with first entry into meiosis, and the phenotype of a fog-1; glp-1 double mutant. Experiments with double mutants show that fog-1 is epistatic to mutations in all other sex-determining genes tested. These results lead to the conclusion that fog-1 acts at the same level as the fem genes at the end of the sex determination pathway to specify germ cells as sperm.

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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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Fluorescence visualization of the distribution of microfilaments in gonads and early embryos of the nematode Caenorhabditis elegans.

The Journal of Cell Biology ◽

10.1083/jcb.103.6.2241 ◽

1986 ◽

Vol 103 (6) ◽

pp. 2241-2252 ◽

Cited By ~ 107

Author(s):

S Strome

Keyword(s):

Caenorhabditis Elegans ◽

Germ Line ◽

Early Stage ◽

Myoepithelial Cells ◽

Nematode Caenorhabditis Elegans ◽

Rhodamine Phalloidin ◽

Early Embryos ◽

Somatic Tissues ◽

Myosin Filaments ◽

Intracellular Motility

Several intracellular motility events in the Caenorhabditis elegans zygote (pseudocleavage, the asymmetric meeting of the pronuclei, the segregation of germ line-specific granules, and the generation of an asymmetric spindle) appear to depend on microfilaments (MFs). To investigate how MFs participate in these manifestations of zygotic asymmetry, the distribution of MFs in oocytes and early embryos was examined, using both antibodies to actin and the F-actin-specific probe rhodamine-phalloidin. In early-stage zygotes, MFs are found in a uniform cortical meshwork of fine fibers and dots or foci. In later zygotes, concomitant with the intracellular movements that are thought to be MF mediated, MFs also become asymmetrically rearranged; as the zygote undergoes pseudocleavage and as the germ line granules become localized in the posterior half of the cell, the foci of actin become progressively more concentrated in the anterior hemisphere. The foci remain anterior as the spindle becomes asymmetric and the zygote undergoes its first mitosis, at which time fibers align circumferentially around the zygote where the cleavage furrow will form. A model for how the anterior foci of actin may participate in zygotic motility events is discussed. Phalloidin and anti-actin antibodies have also been used to visualize MFs in the somatic tissues of the adult gonad. The myoepithelial cells that surround maturing oocytes are visibly contractile and contain an unusual array of MF bundles; the MFs run roughly longitudinally from the loop of the gonad to the spermatheca. Myosin thick filaments are distributed along the MFs in a periodic manner suggestive of a sarcomere-like configuration. It is proposed that these actin and myosin filaments interact to cause sheath cell contraction and the movement of oocytes through the gonad.

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