scholarly journals The Nc1/Endostatin Domain of Caenorhabditis elegans Type Xviii Collagen Affects Cell Migration and Axon Guidance

2001 ◽  
Vol 152 (6) ◽  
pp. 1219-1232 ◽  
Author(s):  
Brian D. Ackley ◽  
Jennifer R. Crew ◽  
Harri Elamaa ◽  
Tania Pihlajaniemi ◽  
Calvin J. Kuo ◽  
...  
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Ectopic Expression ◽  
Basement Membranes ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
C Elegans ◽  
Collagen Xviii ◽  
Nc1 Domain

Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.

Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

2021 ◽  
Author(s):  
Haider Z. Naqvi
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Genetic Background ◽  
Germ Line ◽  
Strong Indication ◽  
Wild Type ◽  
C Elegans ◽  
Novel Gene ◽  
Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

scholarly journals Three C. elegans Rac proteins and several alternative Rac regulators control axon guidance, cell migration and apoptotic cell phagocytosis

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4475-4488 ◽  
Author(s):  
Erik A. Lundquist ◽  
Peter W. Reddien ◽  
Erika Hartwieg ◽  
H. Robert Horvitz ◽  
Cornelia I. Bargmann
Keyword(s):  
Cell Migration ◽  
Axon Guidance ◽  
Apoptotic Cell ◽  
Regulatory Proteins ◽  
Axon Pathfinding ◽  
C Elegans ◽  
Cell Corpse ◽  
And Function ◽  
Redundant Functions ◽  
Caenorhabditis Elegans Genome

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.

A normally attractive cell interaction is repulsive in two C. elegans mesodermal cell migration mutants

Development ◽  
1991 ◽  
Vol 113 (3) ◽  
pp. 797-803 ◽  
Author(s):  
M.J. Stern ◽  
H.R. Horvitz
Keyword(s):  
Cell Migration ◽  
Caenorhabditis Elegans ◽  
Premature Termination ◽  
Cell Interaction ◽  
Egg Laying ◽  
Wild Type ◽  
Mesodermal Cell ◽  
C Elegans ◽  
Somatic Gonad ◽  
Sex Myoblasts

In wild-type Caenorhabditis elegans hermaphrodites, two bilaterally symmetric sex myoblasts (SMs) migrate anteriorly to flank the precise center of the gonad, where they divide to generate the muscles required for egg laying (J. E. Sulston and H. R. Horvitz (1977) Devl Biol. 56, 110–156). Although this migration is largely independent of the gonad, a signal from the gonad attracts the SMs to their precise final positions (J. H. Thomas, M. J. Stern and H. R. Horvitz (1990) Cell 62, 1041–1052). Here we show that mutations in either of two genes, egl-15 and egl-17, cause the premature termination of the migrations of the SMs. This incomplete migration is caused by the repulsion of the SMs by the same cells in the somatic gonad that are the source of the attractive signal in wild-type animals.

scholarly journals The Caenorhabditis elegans homologue of the extracellular calcium binding protein SPARC/osteonectin affects nematode body morphology and mobility.

1993 ◽  
Vol 4 (9) ◽  
pp. 941-952 ◽  
Author(s):  
J E Schwarzbauer ◽  
C S Spencer
Keyword(s):  
Extracellular Matrix ◽  
Caenorhabditis Elegans ◽  
Calcium Binding ◽  
Fusion Gene ◽  
Muscle Cells ◽  
Gene Organization ◽  
The Body ◽  
Matrix Assembly ◽  
Developmentally Regulated ◽  
C Elegans

The extracellular matrix-associated protein, SPARC (osteonectin [Secreted Protein Acidic and Rich in Cysteine]), modulates cell adhesion and induces a change in cell morphology. SPARC expression in mammals is developmentally regulated and is highest at sites of extracellular matrix assembly and remodeling such as parietal endoderm and bone. We have isolated cDNA and genomic DNA clones encoding the Caenorhabditis elegans homologue of SPARC. The gene organization is highly conserved, and the proteins encoded by mouse, human, and nematode genes are about 38% identical. SPARC consists of four domains (I-IV) based on predicted secondary structure. Using bacterial fusion proteins containing nematode domain I or the domain IV EF-hand motif, we show that, like the mammalian proteins, both domains bind calcium. In transgenic nematodes expressing a SPARC-lacZ fusion gene, beta-galactosidase staining accumulated in a striated pattern in the more heavily stained muscle cells along the body. Comparison of the pattern of transgene expression to unc-54-lacZ animals demonstrated that SPARC is expressed by body wall and sex muscle cells. Appropriate levels of SPARC are essential for normal C. elegans development and muscle function. Transgenic nematodes overexpressing the wild-type SPARC gene were abnormal. Embryos were deformed, and adult hermaphrodites had vulval protrusions and an uncoordinated (Unc) phenotype with reduced mobility and paralysis.

scholarly journals Temporal and spatial expression patterns of the small heat shock (hsp16) genes in transgenic Caenorhabditis elegans.

1992 ◽  
Vol 3 (2) ◽  
pp. 221-233 ◽  
Author(s):  
E G Stringham ◽  
D K Dixon ◽  
D Jones ◽  
E P Candido
Keyword(s):  
Caenorhabditis Elegans ◽  
Heat Shock ◽  
Gene Pair ◽  
Expression Patterns ◽  
Developmentally Regulated ◽  
Noncoding Sequences ◽  
C Elegans ◽  
Gene Pairs ◽  
Temporal And Spatial ◽  
Beta Galactosidase

The expression of the hsp16 gene family in Caenorhabditis elegans has been examined by introducing hsp16-lacZ fusions into the nematode by transformation. Transcription of the hsp16-lacZ transgenes was totally heat-shock dependent and resulted in the rapid synthesis of detectable levels of beta-galactosidase. Although the two hsp16 gene pairs of C. elegans are highly similar within both their coding and noncoding sequences, quantitative and qualitative differences in the spatial pattern of expression between gene pairs were observed. The hsp16-48 promoter was shown to direct greater expression of beta-galactosidase in muscle and hypodermis, whereas the hsp16-41 promoter was more efficient in intestine and pharyngeal tissue. Transgenes that eliminated one promoter from a gene pair were expressed at reduced levels, particularly in postembryonic stages, suggesting that the heat shock elements in the intergenic region of an hsp16 gene pair may act cooperatively to achieve high levels of expression of both genes. Although the hsp16 gene pairs are never constitutively expressed, their heat inducibility is developmentally restricted; they are not heat inducible during gametogenesis or early embryogenesis. The hsp16 genes represent the first fully inducible system in C. elegans to be characterized in detail at the molecular level, and the promoters of these genes should find wide applicability in studies of tissue- and developmentally regulated genes in this experimental organism.

scholarly journals The Atypical Rho GTPase CHW-1 Works With SAX-3/Robo to Mediate Axon Guidance in Caenorhabditis elegans

2018 ◽  
Author(s):  
Jamie K. Alan ◽  
Sara Robinson ◽  
Katie Magsig ◽  
Rafael S. Demarco ◽  
Erik A. Lundquist
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Genetic Interaction ◽  
Small Gtpases ◽  
Axon Pathfinding ◽  
Rho Proteins ◽  
C Elegans

AbstractDuring development, neuronal cells extend an axon towards their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the Caenorhabditis elegans (C. elegans) atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. chw-1(Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and crp-1 encodes for a protein that resembles TC10 and TCL. Here, we show that chw-1 works redundantly with crp-1 and cdc-42 in axon guidance. Furthermore, proper levels of chw-1 expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that chw-1 genetically interacts with the guidance receptor sax-3 in PDE neurons. Finally, in VD/DD motor neurons, chw-1 works downstream of sax-3 to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases chw-1 and crp-1 in axon guidance. Furthermore, this is the first evidence of genetic interaction between chw-1 and the guidance receptor sax-3. These data suggest that chw-1 is likely acting downstream and/or in parallel to sax-3 in axon guidance.

scholarly journals Identification Of A Novel Gene Altered In The RQ1 Mutant Strain Affecting Motor Axon Migration In Caenorhabditis Elegans

2021 ◽  
Author(s):  
Haider Z. Naqvi
Keyword(s):  
Caenorhabditis Elegans ◽  
Axon Guidance ◽  
Motor Neurons ◽  
Genetic Background ◽  
Germ Line ◽  
Strong Indication ◽  
Wild Type ◽  
C Elegans ◽  
Novel Gene ◽  
Mutation Region

Novel genetic enhancer screens were conducted targeting mutants involved in the guidance of axons of the DA and DB classes of motor neurons in C. elegans. These mutations are expected in genes that function in parallel to the unc-g/Netrin pathway. The screen was conducted in an unc-5(e53) genetic background and enhancers of the axon guidance defects caused by the absence of UNC-5 were identified. Three mutants were previously identified in the screen called rq1, rq2 and rq3 and two additional mutants called H2-4 and M1-3, were isolated in this study. In order to identify the gene affected by the rq1 mutation, wild-type copies of genes in the mapped rq1 mutation region were injected into the mutants to rescue the phenotypic defects. This is a strong indication that the gene of interest is a novel gene called H04D03.1. Promising results indicate that the H04D03.1 protein also works in germ-line apoptosis.

Differential assembly of alpha- and gamma-filagenins into thick filaments in Caenorhabditis elegans

2000 ◽  
Vol 113 (22) ◽  
pp. 4001-4012 ◽  
Author(s):  
F. Liu ◽  
I. Ortiz ◽  
A. Hutagalung ◽  
C.C. Bauer ◽  
R.G. Cook ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Immunoelectron Microscopy ◽  
Body Wall ◽  
Developmental Stages ◽  
Body Wall Muscle ◽  
Developmentally Regulated ◽  
C Elegans ◽  
Novel Proteins ◽  
Thick Filaments ◽  
Associated Proteins

Muscle thick filaments are highly organized supramolecular assemblies of myosin and associated proteins with lengths, diameters and flexural rigidities characteristic of their source. The cores of body wall muscle thick filaments of the nematode Caenorhabditis elegans are tubular structures of paramyosin sub-filaments coupled by filagenins and have been proposed to serve as templates for the assembly of native thick filaments. We have characterized alpha- and gamma-filagenins, two novel proteins of the cores with calculated molecular masses of 30,043 and 19,601 and isoelectric points of 10.52 and 11.49, respectively. Western blot and immunoelectron microscopy using affinity-purified antibodies confirmed that the two proteins are core components. Immunoelectron microscopy of the cores revealed that they assemble with different periodicities. Immunofluorescence microscopy showed that alpha-filagenin is localized in the medial regions of the A-bands of body wall muscle cells whereas gamma-filagenin is localized in the flanking regions, and that alpha-filagenin is expressed in 1.5-twofold embryos while gamma-filagenin becomes detectable only in late vermiform embryos. The expression of both proteins continues throughout later stages of development. C. elegans body wall muscle thick filaments of these developmental stages have distinct lengths. Our results suggest that the differential assembly of alpha- and gamma-filagenins into thick filaments of distinct lengths may be developmentally regulated.

scholarly journals APLP2 Modulates JNK-Dependent Cell Migration inDrosophila

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Xingjun Wang ◽  
Xiaowei Guo ◽  
Yeqing Ma ◽  
Chenxi Wu ◽  
Wenzhe Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Ectopic Expression ◽  
Basement Membranes ◽  
Exact Role ◽  
Jnk Signaling ◽  
Promote Cell Migration ◽  
Dependent Cell

Amyloid precursor-like protein 2 (APLP2) belongs to the APP family and is widely expressed in human cells. Though previous studies have suggested a role of APLP2 in cancer progression, the exact role of APLP2 in cell migration remains elusive. Here in this report, we show that ectopic expression of APLP2 inDrosophilainduces cell migration which is mediated by JNK signaling, as loss of JNK suppresses while gain of JNK enhances such phenotype. APLP2 is able to activate JNK signaling by phosphorylation of JNK, which triggers the expression of matrix metalloproteinase MMP1 required for basement membranes degradation to promote cell migration. The data presented here unraveled anin vivorole of APLP2 in JNK-mediated cell migration.

scholarly journals The Evolutionary Duplication and Probable Demise of an Endodermal GATA Factor in Caenorhabditis elegans

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 575-588 ◽  
Author(s):  
Tetsunari Fukushige ◽  
Barbara Goszczynski ◽  
Helen Tian ◽  
James D McGhee
Keyword(s):  
Transcription Factor ◽  
Caenorhabditis Elegans ◽  
Zinc Finger ◽  
Specific Binding ◽  
Ectopic Expression ◽  
Intestinal Development ◽  
Wild Type ◽  
C Elegans ◽  
Dna Binding Domains ◽  
Binding Domains

Abstract We describe the elt-4 gene from the nematode Caenorhabditis elegans. elt-4 is predicted to encode a very small (72 residues, 8.1 kD) GATA-type zinc finger transcription factor. The elt-4 gene is located ∼5 kb upstream of the C. elegans elt-2 gene, which also encodes a GATA-type transcription factor; the zinc finger DNA-binding domains are highly conserved (24/25 residues) between the two proteins. The elt-2 gene is expressed only in the intestine and is essential for normal intestinal development. This article explores whether elt-4 also has a role in intestinal development. Reporter fusions to the elt-4 promoter or reporter insertions into the elt-4 coding regions show that elt-4 is indeed expressed in the intestine, beginning at the 1.5-fold stage of embryogenesis and continuing into adulthood. elt-4 reporter fusions are also expressed in nine cells of the posterior pharynx. Ectopic expression of elt-4 cDNA within the embryo does not cause detectable ectopic expression of biochemical markers of gut differentiation; furthermore, ectopic elt-4 expression neither inhibits nor enhances the ectopic marker expression caused by ectopic elt-2 expression. A deletion allele of elt-4 was isolated but no obvious phenotype could be detected, either in the gut or elsewhere; brood sizes, hatching efficiencies, and growth rates were indistinguishable from wild type. We found no evidence that elt-4 provided backup functions for elt-2. We used microarray analysis to search for genes that might be differentially expressed between L1 larvae of the elt-4 deletion strain and wild-type worms. Paired hybridizations were repeated seven times, allowing us to conclude, with some confidence, that no candidate target transcript could be identified as significantly up- or downregulated by loss of elt-4 function. In vitro binding experiments could not detect specific binding of ELT-4 protein to candidate binding sites (double-stranded oligonucleotides containing single or multiple WGATAR sequences); ELT-4 protein neither enhanced nor inhibited the strong sequence-specific binding of the ELT-2 protein. Whereas ELT-2 protein is a strong transcriptional activator in yeast, ELT-4 protein has no such activity under similar conditions, nor does it influence the transcriptional activity of coexpressed ELT-2 protein. Although an elt-2 homolog was easily identified in the genomic sequence of the related nematode C. briggsae, no elt-4 homolog could be identified. Analysis of the changes in silent third codon positions within the DNA-binding domains indicates that elt-4 arose as a duplication of elt-2, some 25–55 MYA. Thus, elt-4 has survived far longer than the average duplicated gene in C. elegans, even though no obvious biological function could be detected. elt-4 provides an interesting example of a tandemly duplicated gene that may originally have been the same size as elt-2 but has gradually been whittled down to its present size of little more than a zinc finger. Although elt-4 must confer (or must have conferred) some selective advantage to C. elegans, we suggest that its ultimate evolutionary fate will be disappearance from the C. elegans genome.

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