WormMine: Gene WBGene00000858

• WormBase Gene ID: WBGene00000858
• Gene Name: cwn-2
• Sequence Name: W01B6.1
• Brief Description: cwn-2 encodes one of five C. elegans Wnt signaling molecules that is homologous to mammalian Wnt5; cwn-2 is required for proper placement of the nerve ring and anterior cells along the anterior/posterior axis; cwn-2 also acts redundantly to specify cell fates during vulval development; CWN-2 appears to be required at the time of nerve ring development (comma stage of embryogenesis) for nerve ring placement and likely functions as a signaling ligand for receptors, such as CAM-1, that regulate axon guidance of the SIA and SIB neurons that plays a role in nerve ring placement; CWN-2, along with LIN-17, CAM-1, and DSH-1, functions as part of a Wnt signaling pathway that regulates ACR-16 localization to postsynaptic regions, a key component of activity-dependent synaptic plasticity; in embryos at the comma stage, a cwn-2::gfp reporter is expressed in the intestine and in pharyngeal muscle; in larvae and adults, cwn-2::gfp is seen in the intestine, pharynx, anterior body wall muscle, vulva and SMD head neurons.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable cytokine activity and frizzled binding activity. Involved in several processes, including neuroblast migration; neuron migration; and pattern specification process. Predicted to be located in extracellular space. Expressed in several structures, including P5.ppp; P7.paa; RME; pharynx; and rectal gland cell. Human ortholog(s) of this gene implicated in several diseases, including autosomal dominant Robinow syndrome 1; endometrial carcinoma; and germ cell cancer (multiple). Is an ortholog of human WNT5A (Wnt family member 5A) and WNT5B (Wnt family member 5B).
• Biotype: SO:0001217
• Genetic Position: IV :4.48175 ±0.001015
• Length (nt): 2436

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00000858

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:W01B6.1.1	W01B6.1.1	1427	IV: 10067816-10070251

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:W01B6.1	W01B6.1	1083	IV: 10067875-10067954

18 RNAi Result

• WBRNAi00101395
• WBRNAi00101343
• WBRNAi00001733
• WBRNAi00054502
• WBRNAi00062823
• WBRNAi00062824
• WBRNAi00097717
• WBRNAi00019448
• WBRNAi00091574
• WBRNAi00030251
• WBRNAi00101704
• WBRNAi00065340
• WBRNAi00098909
• WBRNAi00101448
• WBRNAi00101485
• WBRNAi00101693
• WBRNAi00101688
• WBRNAi00101698

30 Allele

• gk964278
• gk964078
• gk964500
• gk962765
• gk873104
• gk623740
• h11271
• h11935
• gk585702
• gk912347
• gk763977
• gk210117
• gk627684
• gk560645
• gk929305
• WBVar01856593
• gk666612
• WBVar01856592
• gk585701
• WBVar01856596
• ok895
• WBVar01856595
• xd1
• WBVar01856594
• ky736
• ky756
• gk577220
• gk438037
• gk521798
• WBVar01795166

1 Chromosome

• WormBase ID: IV
• Organism: Caenorhabditis elegans
• Length (nt): 17493829

1 Chromosome Location

• Feature . Primary Identifier: WBGene00000858
• Start: 10067816
• End: 10070251
• Strand: 1

4 Data Sets

• WormBaseAcedbConverter
• GO Annotation data set
• C. elegans genomic annotations (GFF3 Gene)
• Panther orthologue and paralogue predictions

0 Downstream Intergenic Region

149 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Transcripts that showed significantly increased expression in L1 neural cells comparing to in adult neural cells.	DESeq2 (v1.18.1) fold change > 2, P-adj<0.05, using BenjaminiHochberg correction.	WBPaper00060811:L1_vs_adult_upregulated_neural
	Transcripts expressed in neuronal cells, by analyzingfluorescence-activated cell sorted (FACS) neurons.	DESeq. False discovry rate (FDR) < 0.1.	WBPaper00048988:neuron_expressed
adult vs dauer larva	Transcripts that showed differential expression in adult vs dauer lava in N2 animals at 20C.	N.A.	WBPaper00050488:adult_vs_dauer_regulated_N2_20C
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_Food
Osmotic stress	Transcripts that showed significantly altered expression with 500 mM salt (NaCl) vs 100 mM salt when no food was present	DESeq(version 1.10.1), FDR < 0.05.	WBPaper00050726:OsmoticStress_regulated_NoFood
	Transcripts expressed in GABAergic neuron, according to PAT-Seq analysis using Punc-47-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:GABAergic-neuron_expressed
	Transcripts that showed significantly decreased expression in atfs-1(cmh15) (null allele) animals comparing to in N2 animals at L4 larva stage.	edgeR, fold change > 2, FDR < 0.05	WBPaper00060909:atfs-1(cmh15)_downregulated
	Transcripts that showed significantly decreased expression in day 3 adult hermaphrodite comparing to in L4 larva daf-16(mu86);glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_daf-16(mu86);glp-1(e2141)
	Transcripts that showed significantly increased expression after four-day-old young adult worms were placed on NGM plates seeded with OP50 in the presence 5% Agaro-oligosaccharides(AGO) for 24 h, comparing to animals grown in the absence of AGO.	Fold change > 2.	WBPaper00064306:Agaro-oligosaccharides_upregulated
	Transcripts that showed significantly increased expression in sin-3(tm1276) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:sin-3(tm1276)_upregulated
	Transcripts that showed significantly changed expression in 6-day post-L4 adult hermaphrodite comparing to in 1-day post L4 adult hermaphrodite animals.	Sleuth	WBPaper00051558:aging_regulated
	Transcripts that showed significantly decreased expression in sin-3(tm1276) comparing to in N2 at early embryo when there were only 3 -5 eggs in the adult.	DESeq2, fold change > 2, adjusted p-value < 0.01	WBPaper00058598:sin-3(tm1276)_downregulated
	Transcripts that showed significantly increased expression in hda-1(ne4752[3xFLAG-Degron-HDA-1]) in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:hda-1(ne4752)_upregulated
	Transcripts that showed significantly increased expression in mep-1(ne4629[MEP-1-GFP-Degron]) in gonads dissected from 1-day old adult animals.	Salmon was used to map the mRNA-seq reads with the worm database WS268, and its output files were imported to DESeq2 in R. The differentially expressed genes were filtered by fold change more than 2 and adjusted p-value < 0.05. The scatter plots were generated by the plot function in R.	WBPaper00061479:mep-1(ne4629)_upregulated
	Transcripts that showed significantly increased expression in hda-2(ok1479) comparing to in N2 animals.	DESeq2 (version 1.28.1), FDR < 0.01, fold change > 2.	WBPaper00062159:hda-2(ok1479)_upregulated
	Transcripts that showed significantly increased expression in srbc-48(ac23);kyIs262;fer-1(b232ts) comparing to in kyIs262;fer-1(b232ts), 24h after infection with P.aeruginosa.	DESeq2, FDR <0.05, fold change > 2.	WBPaper00059664:srbc-48(ac23)_upregulated
	Transcripts that showed significantly altered expression in rnp-6(dh1127) animals comparing to in N2 when fed with live S. aureus.	Differentially expressed genes (DEGs) (q-value <0.05) between different samples were identified using the stringtie version 1.3.0, followed by Cufflinks version 2.2.	WBPaper00059824:rnp-6(dh1127)_regulated_S.aureus
	Transcripts that showed significantly increased expression in animals lacking P granules by RNAi experiments targeting pgl-1, pgl-3, glh-1 and glh-4, and unc-119-GFP(+), comparing to in control animals, at 2-day post L4 adult hermaphrodite stage.	DESeq2, Benjamini-Hochberg multiple hypothesis corrected p-value < 0.05 and fold change > 2.	WBPaper00050859:upregulated_P-granule(-)GFP(+)_vs_control_day2-adult
	Transcripts that showed significantly increased expression in animals lacking P granules by RNAi experiments targeting pgl-1, pgl-3, glh-1 and glh-4, and unc-119-GFP(-), comparing to in control animals, at 2-day post L4 adult hermaphrodite stage.	DESeq2, Benjamini-Hochberg multiple hypothesis corrected p-value < 0.05 and fold change > 2.	WBPaper00050859:upregulated_P-granule(-)GFP(-)_vs_control_day2-adult
	Transcripts of coding genes that showed significantly increased expression in muscle.	DESeq2 (version 1.24.0). Transcripts with a false-discovery rate adjusted p-value less than 0.05 were considered significantly differentially expressed.	WBPaper00062325:muscle_enriched_coding-RNA
	Genes expressed in N2.	Expressed transcripts were identified on the basis of a Present call in 3 out of 4 N2 experiments as determined by Affymetrix MAS 5.0.	WBPaper00025141:N2_Expressed_Genes
	Transcripts that showed significantly increased expression in animals fed with JM103 bacteria producing Cry5B, comparing to control animals fed with JM103.	ANOVA, p-value < 0.05.	WBPaper00056167:Cry5B_upregulated
	Genes uniquely expressed in endoderm, according to RNAseq studies on blastomere (with isolated AB, MS, E, C, D founder cells dividing in vitro) time course and whole embryo time course.	Germ layers were assigned by correlating the average expression with germ-layer-specific patterns with a cutoff of 0.6 correlation with the following idealized vectors: endoderm = [00100]; ectoderm = [10000]; mesoderm = [01011], where the order is AB, MS, E, C and P3. Germ-layer genes were defined according to the sum of the genes identified by the clusters and are indicated in Fig. 2b. Authors further filtered the germ-layer gene sets by keeping only those genes whose expression was partitioned across the germ layers such that at least two-thirds of the expression was in that germ layer.	WBPaper00046121:endoderm_unique
	Embryonic class (E): genes that significantly increase in abundance at some point during embryogenesis.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_E
	Embryonic (E) subclasses are based on the earliest significant increase(abbreviated pi for primary increase).	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_E_pi(122_min)
	Transcripts that showed significantly increased expression in spr-1(ok2144) comparing to in N2.	DESeq2, fold change > 2, p-value < 0.01.	WBPaper00061203:spr-1(ok2144)_upregulated
Dietary restriction	Transcripts that showed significantly increased expression after N2 animals were under dietary restriction (DR, OP50 OD = 0.1) from 3-day post L4 till 6-day post L4 adult hermaphrodite stage, comparing to under ad libtum (AL, OP50 OD = 3) condition.	Bioconductor package edgeR, p < 0.05.	WBPaper00056443:DietaryRestriction_upregulated
	Strictly embryonic class (SE): genes that are the subset of embryonic genes that are not also classified as maternal.	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_SE
	Strictly embryonic (SE) subclasses are based on the earliest significant increase(abbreviated pi for primary increase).	A modified Welch F statistic was used for ANOVA. For each gene, regressed error estimates were substituted for observed error estimates. The substitution is justified by the lack of consistency among the most and least variable genes at each time point. Regressed error estimates were abundance-dependent pooled error estimates that represented a median error estimate from a window of genes of similar abundance to the gene of interest. A randomization test was used to compute the probability Pg of the observed F statistic for gene g under the null hypothesis that developmental time had no effect on expression. P-values were not corrected for multiple testing.	[cgc5767]:expression_class_SE_pi(122_min)
	Transcripts that showed significantly decreased expression in pals-22(jy3) comparing to in N2 animals.	limma-voom, fold change > 2, FDR < 0.05	WBPaper00064532:pals-22(jy3)_downregulated

16 Expression Patterns

• Primary Identifier: Expr1019538
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr1030530
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr13820
• Pattern: Consistent with previous findings, Pcwn-2::GFP is expressed beginning in early embryonic stages, mainly in the digestive and nervous systems, with weak expression in the body wall muscles at adult stage. The GFP reporter is only seen in the intestine before 2-fold stage. In late embryonic stage, Pcwn-2::GFP is expressed both in the intestine and the pharynx. After hatching, Pcwn-2::GFP is mainly seen in the pharynx, some head neurons, the body wall muscle and the intestine. However, Pcwn-2::GFP is not seen in the AIY.

• Primary Identifier: Expr9885
• Reporter Gene: [cwn-2p::CWN-2::Venus] translational fusion. cwn-2p::CWN-2::Venus was constructed from PCR fragments containing its promoter region (6.1 kb), and the entire coding region was amplified by PCR from the fosmid WRM0622bE06 inserted into a pPD95.75::wVenus derived from pPD95.75 (a gift from A. Fire) and containing the Venus gene optimized for C. elegans codon usage in place of the GFP gene. --precise ends.
• Pattern: We detected puncta of cwn-2p::CWN-2::Venus mostly around the pharynx. We detected these puncta on the hypodermis, including the seam cells, suggesting its diffusion from the pharyngeal region. Although it was also reported that the cwn-2 promoter is active in the intestine, albeit weaker than in the pharynx, we detected cwn-2p::CWN-2::Venus puncta only in the anterior region, along the boundary between the intestine and muscle or hypodermis. These observations indicate that CWN-2 is mostly distributed to the anterior side of the animal.

• Primary Identifier: Expr7987
• Remark: Picture: Figure 2, Figure S4.
• Pattern: cwn-2 expression was observed in early embryos, at approximately 0-2 hours after egg laying, and continued throughout embryonic and larval development. In larvae, the expression pattern of cwn-2 is very similar to that of cwn-1 with one notable exception. While cwn-1 is expressed predominately in the posterior half of the animal in VCNs and BWMs, cwn-2 is expressed along the length of the anterior-posterior body axis. Expression of cwn-2 was also observed in intestinal nuclei. In L4 larvae, cwn-2 was observed in P5.p to P7.p descendants. In adults, expression of cwn-2 was only observed in BWMs.

• Primary Identifier: Expr9346
• Pattern: cwn-2 transcripts mainly localized to head neurons, anterior body wall muscle cells, anterior P.n cells and the intestine. The highest cwn-2 transcript count was observed around the terminal bulb of the pharynx, with a gradual decline in expression levels in more posterior cells. The mostly anterior expression of cwn-2 and posterior expression of cwn-1 was already observed at the 100-cell stage of embryonic development.

• Primary Identifier: Expr11629
• Remark: Temporal description.
• Pattern: Pcwn-2::mCherry signal first appeared in the intestine before the expression of Punc-25::GFP during embryogenesis. At late embryonic stage when RMED/V neurite start extending posteriorly, the highest expression of CWN-2 is found at posterior pharyngneal bulb and the pharyngeal-intestinal valve. When animals are at L1 stage, the RMED/V neurites grow towards the posterior pharynx, where CWN-2 displays relatively higher expression level. The expression pattern of CWN-2 at both embryonic and L1 stages correlates well with the attractant role of CWN-2 during neurite outgrowth. After L1 stage, the neurites continue their growth and pass the posterior pharynx; meanwhile CWN-2 is also found expressed in body muscles and some ventral cord neurons.

• Primary Identifier: Expr8833
• Remark: Picture: Fig 3A, 3B, 3C. Reporter gene fusion type not specified.
• Pattern: At the comma stage of embryonic development when the nerve ring forms, cwn-2::SL2::GFP was expressed in the developing intestine and pharyngeal muscle, which are posterior to the developing nerve ring. The overall expression pattern was maintained in larval and adult stages, with cwn-2::SL2::GFP expression in intestine, pharynx, anterior body wall muscle, vulva and SMD head neurons.

• Primary Identifier: Expr12035
• Pattern: cwn-2::GFP was observed in some rectal gland cells.

• Primary Identifier: Expr11179
• Pattern: Expression of cwn-2 Wnt ligand decreases during aging. The cwn-2/Wnt expression was observed all along the anterior-posterior body axis of the animal in body-wall muscles. The authors did not detect any expression in ventral cord motor neurons or intestinal cells as was previously observed during worm development (Gleason et al. 2006). By qPCR the authors found that total expression levels for both Wnt ligands significantly increased between day 2 and 5 of adulthood. In addition, expression of mom-2/Wnt is highly increased in posterior intestinal cells, but remains unchanged or may be even decreased in other tissues, where the authors failed to detect any expression using their transcriptional reporters.

• Primary Identifier: Expr2010638
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

• Primary Identifier: Expr15699
• Pattern: To determine the protein localization of these Wnt ligands, we tagged them with YFP using a fosmid reporter strategy. Interestingly, the CWN-1::YFP and CWN-2::YFP proteins are detectable in the region where the SMDD/AIY mother cell is present, anterior to their source. This suggests that CWN-1 and CWN-2 move away from their posterior source to the SMDD/AIY mother area. For MOM-2::YFP, the fluorescence levels are too low to conclude.

• Primary Identifier: Expr2028878
• Pattern: Single cell embryonic expression. Only cell types with an expression fraction of greater 0.2 of the maximum expressed fraction are labeled (Full data can be downloaded from http://caltech.wormbase.org/pub/wormbase/datasets-published/packer2019/). The colors represent the broad cell class to which the cell type has been assigned. The size of the point is proportional to the log2 of the numbers of cells in the dataset of that cell type. Interactive visualizations are available as a web app (https://cello.shinyapps.io/celegans/) and can also be installed as an R package (https://github.com/qinzhu/VisCello.celegans).

• Primary Identifier: Expr15695
• Pattern: Using transcriptional reporters of the five Wnt ligands [cis-regulatory elements of the Wnt ligands placed upstream of a nuclear GFP (Gleason et al., 2006)], we observed that three Wnt ligands (CWN-1, CWN-2 and MOM-2) are expressed in the embryo at the time of the terminal division of the SMDD/AIY mother cell. We could not detect expression of the two remaining Wnt ligands (LIN-44 and EGL-20) at that time but start seeing expression at later stages, during elongation, in the posterior end of the embryo. Interestingly, at the time of the terminal division of the SMDD/AIY mother cell, cwn-1, cwn-2 and mom-2 are transcribed at a higher level in the posterior region of the embryo than in the anterior region. These observations are consistent with an analysis of the transcription pattern of Wnt ligands by fluorescent in situ hybridization (Harterink et al., 2011). cwn-1, cwn-2 and mom-2 are transcribed in several tissues: cwn-1 (posterior muscle), cwn-2 ( posterior neuronal progenitors, posterior epidermis, intestine and posterior muscle) and mom-2 (posterior epidermis and muscle). Their zygotic expression starts during gastrulation and remains during embryonic elongation.

• Primary Identifier: Expr1158049
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr739
• Remark: Also called wnt-2 in the article. Similar expression to cwn-1/Ce-wnt-1. Levels decreasing more rapidly than Ce-wnt-1 during successive stages of development and do not increase in late larval stages. This information was extracted from published material (Archana Sharma-Oates, Andrew Mounsey and Ian A. Hope).
• Pattern: 1.5 kb RNA transcript abundant in embryos. Lower levels present in larval and adult stages. Lowest level in immature and gravid adults.

52 GO Annotation

9 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00000858
• Start: 10067816
• End: 10070251
• Strand: 1

52 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 2436

1 Sequence Ontology Term

• Name: gene

21 Strains

• WBStrain00035939
• WBStrain00035437
• WBStrain00035435
• WBStrain00035439
• WBStrain00035444
• WBStrain00035443
• WBStrain00035442
• WBStrain00035448
• WBStrain00035447
• WBStrain00035446
• WBStrain00035445
• WBStrain00035449
• WBStrain00035450
• WBStrain00008496
• WBStrain00008497
• WBStrain00008503
• WBStrain00007454
• WBStrain00007457
• WBStrain00007444
• WBStrain00007453
• WBStrain00007443

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrIV_10062850..10067815
• Length (nt): 4966
• Chromosome Location: IV: 10062850-10067815
• Organism: Caenorhabditis elegans