Skiba F et al. (1991) International C. elegans Meeting "EMBRYOGENESIS OF FREE-LIVING AND PARASITIC NEMATODES."

Spieler M, Schierenberg E, Skiba F

[International C. elegans Meeting, 1991]

To obtain a better idea of basic developmental strategies, we isolated a variety of species from the soil, cultured them on agar plates and studied their embryogenesis. The basic scheme is similar in all strains but considerable differences in detail were found. At 16 C early embryogenesis takes 14x longer in the slowest than in the fastest strain. The slower embryogenesis proceeds, the relatively earlier cleavage of germline cells takes place. While in the fastest strain (C. eleqans) the primordial germ cell is present in the 24-cell stage, in the slowest strain it is already generated in the 5-cell stage. We suggest that germline cells have to cleave within a certain time limit to allow preservation of their potential. The typical reversal of cleavage polarity in the germline cell P2 is absent in the slowest, apparently more primitive strain leading to abnormal arrangement of cells. However, as a result of compensatory cell migrations a common pattern is reached in all strains at the onset of gastrulation which may be a prerequisite for proper development. In about half of our strains cytoplasmic and/or nuclear structures can be visualized with a MAB against P granules of C. elegans. Our results do not support the notion that similar staining pattern indicates close phylogenetic relationship. In cooperation with Susan Strome, Bloomington, we have started to analyze cleavage of the ts mutant mes1 (bn7). At restrictive temperature reversal of polarity in P2 appears to be absent as described above. How this relates to the grandchildless effect remains to be determined. Studying embryogenesis of Rhabdias bufonis, a nematode with alternating parasitic and free- living generations, our preliminary data indicate considerable differences in timing and order of cleavages in consecutive generations.

Skiba F et al. (1990) Worm Breeder's Gazette "ABSENT REVERSAL OF CLEAVAGE POLARITY IN A FREE-LIVING NEMATODE"

Schierenberg E, Skiba F

[Worm Breeder's Gazette, 1990]

As reported in WBG 11(1) we have started a comparative analysis of embryogenesis in a number of free-living soil nematodes. Besides other aspects we tested whether our strains all express the typical reversal of cleavage polarity in the germline cell P2. While after the division of P0 and P1 the new germline cell comes to lie posterior of its somatic sister, it is the other way round after cleavage of P2 and P3 (see scheme below; for details, see Schierenberg,1987, Dev. Biol. 122,452). In the course of our studies we found two species in which this reversal of polarity does not take place. One of these is Cephalobus spec. which belongs to the order Rhabditida as do all of our studied strains including C. elegans ( only species of this order appear to survive under our standard laboratory conditions). Cephalobus is slowest of all our strains. Its early development is 14x slower than C. elegans (at 16 C). However, development accelerates with increasing temperature but never comes close to C. elegans. The maximal temperature at which we get well reproducing Cephalobus is 35 C (C. elegans 26 C). The fact that in Cephalobus the whole series of unequal germline cleavages is completed at the 6-cell stage (C. elegans: 24-cells) has been shown in the above mentioned WBG. Because of this altered division sequence but also because of the missing cleavage reversal in the germline (see scheme below) an unusual spatial pattern of cells is generated. By compensating migrations a pattern similar to C. elegans is reached prior to gastrulation. With the antibody L-416 against germline-specific P granules courtesy of Susan Strome) in Cephalobus nuclei in all somatic cells can be marked, while in the germline only the perinuclear region appears to react positively. From the data we have collected we assume that Cephalobus represents a more primitive (original?) species than C. elegans.Below a scheme ( drawn from a photo series) is given demonstrating the missing polarity reversal. For better visualization some cells have been removed from the anterior pole of both embryos. [See Figure 1]

Skiba F et al. (1989) Worm Breeder's Gazette "comparative analysis of early embryogenesis in different free-living nematode strains."

Skiba F, Schierenberg E

[Worm Breeder's Gazette, 1989]

We have collected soil from places as near as the institute backyard and as far as the mountains of Peru. From these probes we have isolated different nematode strains and have cultured those which happened (or got used) to grow on our standard agar plates. With the help of Dr. Sudhaus, Berlin, we have characterized them phenotypically. They probably represent 16 different species which all belong to the order 'Rhabditida'. By the criteria of outer inspection one of them appears to be a 'C. elegans', but a cross- fertilization test needs to be done. The adults of all strains are about 1-2 mm long and vary considerably in diameter. Most of them express a life cycle several-fold longer than that of C. elegans, none of them is faster. About half of them are self-fertilizing hermaphrodites. We have analyzed early cell lineages up to the 50- cell stage and have compared them to those of C. elegans. All strains express the typical pattern of nematode cleavage, whereby somatic founder cells (AB,HS,E,C,D) are generated in a series of unequal germline cleavages. In detail, however, variations were found which essentially concern the timing of cell divisions in the germline. Those strains which come closest to C. elegans in speed of developmental events also express the same sequence of early cleavages. In those strains with a slower developmental rhythm, divisions in the germline cells P1- P3 take place relative too early. In general, the following correlation was found: The slower embryogenesis proceeds in a certain strain, the earlier germline cleavages occur in the sequence of dividing blastomeres (see figure below). In our slowest strain (Cephalobus spec. from Peru) P4 is present already in the 6- cell stage, compared to the 24-cell stage in C. elegans. Altered sequence of cleavages leads to early cell patterns different from those in C. elegans. By the 24-cell stage, however, spatial organization of cells has become essentially the same in all strains. Our findings are consistent with the view that germline cells have to cleave within a certain time limit to preserve (or obtain) their specific identity as suggested by the cib-mutants (R. & H. Schnabel, pers. communication). Testing with an antibody against C. elegans P granules, we found that about 50% of the strains showed P granule staining. So far, we have no indication that these results reflect phylogenetic relationships. In no case we detected chromatin diminution. [See Figure 1]

Skiba F et al. (1992) Dev Biol "Cell lineages, developmental timing, and spatial pattern formation in embryos of free-living soil nematodes."

Skiba F, Schierenberg E

[Dev Biol, 1992]

From soils of various origins we have isolated a number of nematode strains and cultured them on agar plates. We have analyzed their anatomy, reproduction, and particularly their pattern of embryogenesis. With respect to early cleavage we can define six different classes. The basic scheme of embryogenesis is similar in all strains but considerable differences were observed in detail. Embryogenesis is more than five times longer in the slowest strain than in the fastest. The following general correlation was found: The slower embryogenesis proceeds in a strain, the relatively earlier the cleavage of germline cells occurs. In the fastest strain the primordial germ cell P4 is present at the 24-cell stage, while in the slowest strain it is already generated in the 5-cell stage. We hypothesize that germline cleavages have to occur within a certain time limit to preserve germline quality. The typical reversal of cleavage polarity in the division of the germline cell P2 is absent in the slowest, on other grounds apparently more primitive strain. This results in an unusual spatial arrangement of cells transiently. However, prior to gastrulation as a consequence of compensatory cell migrations (which may indicate the necessity for cell interactions), the pattern becomes very similar to that in the other strains. We propose that a standard cellular configuration is required at the beginning of gastrulation to ensure normal further development. Early cell interactions might be necessary to achieve this standard pattern. In about half of the analyzed strains cellular structures can be marked with an antibody raised against germline-specific granules of Caenorhabditis elegans. Our results do not support the notion that the staining pattern for P granules is a useful indicator for phylogenetic relationship.

Kipreos ET et al. (2000) Genome Biol "The F-box protein family."

Kipreos ET, Pagano M

[Genome Biol, 2000]

SUMMARY: The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. F-box proteins were first characterized as components of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin, and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis. The F-box motif links the F-box protein to other components of the SCF complex by binding the core SCF component Skp I. F-box proteins have more recently been discovered to function in non-SCF protein complexes in a variety of cellular functions. There are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal motifs capable of protein-protein interaction; the most common secondary motifs in yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which have been found to bind phosphorylated substrates to the SCF complex. The majority of F-box proteins have other associated motifs, and the functions of most of these proteins have not yet been defined.

Chamberlin HM et al. (1995) Worm Breeder's Gazette "lin-49, An Essential Gene Required For Normal F and U Cells."

Chamberlin HM, Sternberg PW, Baillie DL

[Worm Breeder's Gazette, 1995]

lin-49, an essential gene required for normal F and U cells

Bennett JL et al. (1988) Parasitol Today "Pharmacology of ivermectin."

Williams JF, Bennett JL, Dave V

[Parasitol Today, 1988]

Ivermectin is a semi-synthetic macrocyclic lactone (Fig. I) active in single low doses against many parasites - particularly nematodes and arthropods. It has been registered for animal health use since early 1985, and was earlier this year approved for human use by the French Directorate o f Pharmacy and Drugs. Of particular interest is ivermectin's potential as a micro filaricide for treatment o f onchocerciasis. Clinical trials leave little doubt about the potential o f ivermectin as a therapeutic tool for symptomatic relief from the effects o f infection with Onchocerca volvulus, and the drug is also recognized to have potential in reducing transmission o f the parasite. The manufacturers (Merck, Sharp and Dohme) recently arranged to provide the drug free o f charge to the WHO for mass trials against onchocerciasis in 12 African and Central American countries. In this article we focus on the pharmacological properties o f ivermectin, with a brief consideration of its absorption, fate, excretion and side-effects, and a discussion o f its micro filaricidal action.

Rehain K et al. (2015) Curr Biol "Neuron migration: anillin protects leading edge actin."

Maddox AS, Rehain K

[Curr Biol, 2015]

Establishment of a neuronal system requires proper regulation of the F-actin-rich leading edges of migrating neurons and neurite growth cones. A new study shows that RhoG signals through the multi-domain protein anillin to stabilize F-actin in these structures.

Kwiatkowski AV et al. (2010) Proc Natl Acad Sci U S A "In vitro and in vivo reconstitution of the cadherin-catenin-actin complex from Caenorhabditis elegans."

Hardin J, Weis WI, Nelson WJ, Choi HJ, Lynch AM, Kwiatkowski AV, Benjamin JM, Pokutta S, Maiden SL

[Proc Natl Acad Sci U S A, 2010]

The ternary complex of cadherin, beta-catenin, and alpha-catenin regulates actin-dependent cell-cell adhesion. alpha-Catenin can bind beta-catenin and F-actin, but in mammals alpha-catenin either binds beta-catenin as a monomer or F-actin as a homodimer. It is not known if this conformational regulation of alpha-catenin is evolutionarily conserved. The Caenorhabditis elegans alpha-catenin homolog HMP-1 is essential for actin-dependent epidermal enclosure and embryo elongation. Here we show that HMP-1 is a monomer with a functional C-terminal F-actin binding domain. However, neither full-length HMP-1 nor a ternary complex of HMP-1-HMP-2(beta-catenin)-HMR-1(cadherin) bind F-actin in vitro, suggesting that HMP-1 is auto-inhibited. Truncation of either the F-actin or HMP-2 binding domain of HMP-1 disrupts C. elegans development, indicating that HMP-1 must be able to bind F-actin and HMP-2 to function in vivo. Our study defines evolutionarily conserved properties of alpha-catenin and suggests that multiple mechanisms regulate alpha-catenin binding to F-actin.

Wang A et al. (2021) BMC Genomics "Genome-wide characterization, evolution, structure, and expression analysis of the F-box genes in Caenorhabditis."

Chen W, Tao S, Wang A

[BMC Genomics, 2021]

Background: F-box proteins represent a diverse class of adaptor proteins of the ubiquitin-proteasome system (UPS) that play critical roles in the cell cycle, signal transduction, and immune response by removing or modifying cellular regulators. Among closely related organisms of the Caenorhabditis genus, remarkable divergence in F-box gene copy numbers was caused by sizeable species-specific expansion and contraction. Although F-box gene number expansion plays a vital role in shaping genomic diversity, little is known about molecular evolutionary mechanisms responsible for substantial differences in gene number of F-box genes and their functional diversification in Caenorhabditis. Here, we performed a comprehensive evolution and underlying mechanism analysis of F-box genes in five species of Caenorhabditis genus, including C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei.Results: Herein, we identified and characterized 594, 192, 377, 39, 1426 F-box homologs encoding putative F-box proteins in the genome of C. brenneri, C. briggsae, C. elegans, C. japonica, and C. remanei, respectively. Our work suggested that extensive species-specific tandem duplication followed by a small amount of gene loss was the primary mechanism responsible for F-box gene number divergence in Caenorhabditis genus. After F-box gene duplication events occurred, multiple mechanisms have contributed to gene structure divergence, including exon/intron gain/loss, exonization/pseudoexonization, exon/intron boundaries alteration, exon splits, and intron elongation by tandem repeats. Based on high-throughput RNA sequencing data analysis, we proposed that F-box gene functions have diversified by sub-functionalization through highly divergent stage-specific expression patterns in Caenorhabditis species.Conclusions: Massive species-specific tandem duplications and occasional gene loss drove the rapid evolution of the F-box gene family in Caenorhabditis, leading to complex gene structural variation and diversified functions affecting growth and development within and among Caenorhabditis species. In summary, our findings outline the evolution of F-box genes in the Caenorhabditis genome and lay the foundation for future functional studies.