WormMine: Gene WBGene00002992

• WormBase Gene ID: WBGene00002992
• Gene Name: lin-3
• Sequence Name: F36H1.4
• Brief Description: lin-3 encodes a member of the EGF family of peptide growth factors that affects induction of vulval development, viability, ovulation, behavioral quiescence after stress, and male spicule development; it acts genetically upstream of its presumptive receptor let-23, and is expressed in multiple locations consistent with it acting as a localized ligand; for example, the anchor cell of the developing gonad, which induces vulval development.
• Organism: Caenorhabditis elegans
• Automated Description: Enables receptor ligand activity. Involved in several processes, including egg-laying behavior; positive regulation of ovulation; and positive regulation of vulval development. Located in plasma membrane. Expressed in several structures, including excretory canal; germ line; hermaphrodite gonad; rectal epithelial cell; and vulF.
• Biotype: SO:0001217
• Genetic Position: IV :4.82027 ±0.004649
• Length (nt): 9461

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00002992

Genomics

11 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:F36H1.4g.1	F36H1.4g.1	1549	IV: 11054308-11063171
Transcript:F36H1.4b.2	F36H1.4b.2	1944	IV: 11054308-11063650
Transcript:F36H1.4c.1	F36H1.4c.1	1869	IV: 11054308-11063614
Transcript:F36H1.4h.1	F36H1.4h.1	1996	IV: 11054308-11063747
Transcript:F36H1.4a.1	F36H1.4a.1	2035	IV: 11054310-11063737
Transcript:F36H1.4h.2	F36H1.4h.2	1805	IV: 11057664-11063611
Transcript:F36H1.4d.1	F36H1.4d.1	2085	IV: 11057664-11063768
Transcript:F36H1.4b.1	F36H1.4b.1	1790	IV: 11057670-11063557
Transcript:F36H1.4b.3	F36H1.4b.3	1338	IV: 11057787-11063171
Transcript:F36H1.4f.1	F36H1.4f.1	1434	IV: 11057814-11063171
Transcript:F36H1.4e.1	F36H1.4e.1	1299	IV: 11059299-11063171

Other

8 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:F36H1.4b	F36H1.4b	1311	IV: 11057814-11057868
CDS:F36H1.4d	F36H1.4d	1389	IV: 11057814-11057868
CDS:F36H1.4f	F36H1.4f	1434	IV: 11057814-11057868
CDS:F36H1.4e	F36H1.4e	1299	IV: 11059299-11059341
CDS:F36H1.4a	F36H1.4a	1317	IV: 11057814-11057868
CDS:F36H1.4c	F36H1.4c	1272	IV: 11057814-11057868
CDS:F36H1.4g	F36H1.4g	1395	IV: 11057814-11057868
CDS:F36H1.4h	F36H1.4h	1266	IV: 11057814-11057868

54 RNAi Result

• WBRNAi00107721
• WBRNAi00107722
• WBRNAi00067079
• WBRNAi00067115
• WBRNAi00067180
• WBRNAi00067283
• WBRNAi00067340
• WBRNAi00067584
• WBRNAi00067602
• WBRNAi00067638
• WBRNAi00001663
• WBRNAi00057789
• WBRNAi00062583
• WBRNAi00030244
• WBRNAi00072469
• WBRNAi00072468
• WBRNAi00078383
• WBRNAi00085569
• WBRNAi00072467
• WBRNAi00068451
• WBRNAi00068453
• WBRNAi00068452
• WBRNAi00068455
• WBRNAi00068454
• WBRNAi00064503
• WBRNAi00064583
• WBRNAi00064635
• WBRNAi00074293
• WBRNAi00074292
• WBRNAi00074295

126 Allele

• gk964278
• gk964078
• gk964500
• gk962765
• WBVar02123093
• WBVar02124207
• s751
• s1263
• s1750
• sy51
• sy52
• sy91
• sy53
• gk946617
• WBVar01828134
• h17790
• h13757
• h6642
• h17977
• mf72
• mf73
• mf74
• mf75
• mf90
• WBVar00236607
• n1058
• n1059
• WBVar01857722
• WBVar01857723
• WBVar01857724

1 Chromosome

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

1 Chromosome Location

• Feature . Primary Identifier: WBGene00002992
• Start: 11054308
• End: 11063768
• Strand: 1

3 Data Sets

• WormBaseAcedbConverter
• GO Annotation data set
• C. elegans genomic annotations (GFF3 Gene)

0 Downstream Intergenic Region

159 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	Genes with expression altered >= 3-fold in dpy-10(e128) mutants.	Data across the wild type series was analyzed using the Significance analysis of Microarrays (SAM) algorithm (to calculate the False Discovery Rate (FDR)).	WBPaper00035873:dpy-10_regulated
	Transcripts of coding genes that showed significantly decreased 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_depleted_coding-RNA
	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
	mRNAs that showed decreased expression in 1 cell mebryo comparing to in oocyte, according to RNAseq analysis.	Gaussian error propagation. As cutoff for the up-regulated genes authors used log2 fold change > 1 and P < 0.05 and as cutoff for the down-regulated genes authors used log2 fold change < -1 and P < 0.05.	WBPaper00045420:fertilization_downregulated_transcript
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
	Genes that were upregulated in lin-15B(n744).	For each gene in each microarray hybridization experiment, the ratio of RNA levels from the two samples was transformed into a log2 value and the mean log2 ratio was calculated. The log2 ratios were normalized by print-tip Loess normalization (Dudoit and Yang, 2002). All genes with a false discovery rate of <= 5% (q <= 0.05) (Storey and Tibshirani, 2003) and a mean fold-change ratio of >= 1.5 were selected for further analysis.	WBPaper00038168:lin-15B(n744)_upregulated
	Genes that showed significantly increased expression in wrn-1(gk99) comparing to in N2, according to RNAseq.	DESeq was used to calculate the fold changes, log fold changes, and significance of the changes for each comparison.	WBPaper00045934:wrn-1(gk99)_upregulated
	Transcripts expressed in body muscle, according to PAT-Seq analysis using Pmyo-3-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:body-muscle_expressed
	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
	Maternal class (M): genes that are called present in at least one of the three PC6 replicates.	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_M
	Transcripts expressed in pharynx, according to PAT-Seq analysis using Pmyo-2-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:pharynx_expressed
	Genes with expression level regulated by genotype (N2 vs CB4856) and age at old adults stage (214 hours at 24 centigrade).	For model 2, authors used 100 permutations to estimate the FDR threshold. Per permutation, genotypes and ages were independently randomly distributed, keeping the among-gene structure intact. Then for each spot (23,232) on the array, model 2 was tested. The obtained P-values were used to estimate a threshold for each of the explanatory factors. Authors also used a genome-wide threshold of -log10 P-value = 2, which resembles an FDR of 0.072 and 0.060 for marker and the interaction age-marker for the developing worms and FDR of 0.050 and 0.065 for marker and age-marker for the aging worms. For the physiological age effect, authors used a log10 P-value = 8 in developing worms (0.012 FDR) and -log10 P-value = 6 (0.032 FDR).	WBPaper00040858:eQTL_age_regulated_aging
	Transcripts that showed significantly increased expression in day 1 adult hermaphrodite comparing to in L4 larva glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-1-adult_vs_L4_upregulated_glp-1(e2141)
	Strictly maternal class (SM): genes that are the subset of maternal genes that are not also classified as embryonic.	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_SM
Bacteria diet: Sphingomonas aquatilis Yellow. Fed for 30 generations.	Transcripts that showed significantly decreased expression after fed by bacteria Sphingomonas aquatilis (Yellow) for 30 generations comparing to animals fed by E. coli OP50.	DESeq2 fold change > 2, p-value < 0.01.	WBPaper00061007:S.aquatilis_downregulated
	Transcripts that showed significantly decreased expression in hsp-6(mg585) comparing to in N2 at L4 larva stage.	EdgeR, fold change > 2, FDR < 0.001.	WBPaper00056290:hsp-6(mg585)_downregulated
	Transcripts that showed significantly increased expression in animals exposed to 400uM tamoxifen from L1 to L4 larva stage.	DEseq2, fold change > 2	WBPaper00064505:tamoxifen_upregulated
	Transcripts that showed significantly altered expression after 24 hour exposure to stavudine (d4T) starting at L1 lava stage.	DESeq	WBPaper00053302:stavudine_24h_regulated
25C vs. 20C	Transcripts that showed significantly increased expression in 1-day post L4 adult hermaphrodite N2 grown at 25C, comparing to in N2 animals grown at 20C.	CuffDiff, fold change > 2.	WBPaper00065096:25C_vs_20C_upregulated
	Transcripts that showed significantly increased expression in 10-days post L4 adult hermaphrodite N2 grown at 20C, comparing to in 1-day post L4 adult hermaphrodite N2 animals grown at 20C.	CuffDiff, fold change > 2.	WBPaper00065096:Day10_vs_Day1_upregulated
	Transcripts that showed significantly decreased expression in tetraploid N2 comparing to diploid N2 animals at L4 larva stage.	DESeq2 R package (1.20.0), fold change > 2, and FDR < 0.05.	WBPaper00066110:tetraploid_vs_diploid_downregulated
	Genes that showed expression levels higher than the corresponding reference sample (L2 all cell reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:coelomocytes_L2-larva_expressed
	Genes that showed expression levels higher than the corresponding reference sample (L3/L4 all cell reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:dopaminergic-neurons_L3-L4-larva_expressed
	Genes that showed expression levels higher than the corresponding reference sample (embryonic 0hr reference).	A Mann-Whitney U test with an empirical background model and FDR correction for multiple testing was used to detect expressed transcripts (Benjamini and Hochberg 1995). Genes and TARs with an FDR <= 0.05 were reported as expressed above background. Authors detected differentially expressed transcripts using a method based on linear models. Genes and TARs were called differentially expressed if the FDR was <= 0.05 and the fold change (FC) >= 2.0. To more strictly correct for potential false-positives resulting from multiple sample comparisons, authors divided individual FDR estimates by the number of samplesor sample comparisons, respectively. This resulted in an adjusted FDR of 1.3 * 0.0001 for expression above background and of 7.4 * 0.0001 for differential expression. Authors called genes selectively enriched in a given tissue if they met the following requirements: (1) enriched expression in a given tissue (FDR <= 0.05 and FC >= 2.0), (2) fold change versus reference among the upper 40% of the positive FC range observed for this gene across all tissues, and (3) fold-change entropy among the lower 40% of the distribution observed for all genes.	WBPaper00037950:germline-precursors_blastula-embryo_expressed
	Transcripts that showed significantly increased expression in ilc-17.1(syb5296) comparing to in N2 animals at L4 larva stage.	DESeq2, fold change > 2, FDR < 0.05.	WBPaper00066594:ilc-17.1(syb5296)_upregulated
	Transcripts that showed significantly increased expression in dpy-21(e428) comparing to in N2 during L3 stage.	DESeq v1.6.3. Fold change > 1.5.	WBPaper00050370:dpy-21(e428)_L3_upregulated
	Transcripts that showed significantly increased expression in hira-1(gk835598) comparing to in N2 animals at L4 larva stage.	Differential expression analysis was done with Rversion 2.15.3 using DESeq_1.10.1. Fold change > 2, p-value < 0.01.	WBPaper00059739:hira-1(gk835598)_upregulated_L4
	Transcripts that showed significantly decreased expression after animals were treated with 50uM Rifampicin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin_downregulated
	Transcripts that showed significantly decreased expression in nhl-2(ok818) comparing to in N2 at 25C.	EdgeR, FDR < 0.05, fold change < 0.5.	WBPaper00055971:nhl-2(ok818)_25C_upregulated

16 Expression Patterns

• Primary Identifier: Expr1031391
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Marker78
• Remark: Picture: N.A.
• Pattern: Marker for anchor cell.

• Primary Identifier: Expr2894
• Remark: Reporter gene fusion type not specified.
• Pattern: The longest construct, containing 10 kb of 5 upstream region from the first lin-3 exon, expresses lin-3::gfp in pharynx; spermathecal-uterine junction core cells and later in the spermatheca valve; pre-anchor (AC)/ventral uterine precursor (VU) cells and later in the anchor cell in the somatic gonad; vulF cells of the primary vulval lineage cells; and F, U and some of the B progeny cells in the male tail. This expression pattern was not affected by the different genetic backgrounds (dpy-20, pha-1 and unc-119) rescued by the corresponding co-injected rescue plasmids, implying that the gfp expression pattern is established by the lin-3 regulatory region. LIN-3 expression in different cells was temporally distinct as well. Expression in the pharynx was observed throughout post-embryonic stages. Spermathecal-uterine junction core cells, which later form the spermatheca valve, started expressing lin-3::gfp at the late L3 larval stage.

• Primary Identifier: Expr9352
• Pattern: During larval stages, LIN-3 expression was detected in the pharynx and the anchor cell using a nuclear-localized GFP reporter. The expression of LIN-3 protein becomes detectable in intestinal and hypodermal cells as animals mature into fertile adults (24h post-L4 onwards).

• Primary Identifier: Expr9878
• Pattern: The expression pattern of lin-3 in wild-type animals was determined at the late L2 to early L3 stage when vulval induction occurs. Robust expression of lin-3 was observed in the anchor cell and throughout the pharynx. Expression of lin-3 was also seen in the germline. In some wild-type animals a few copies of lin-3 mRNA were seen in one or more cells in the tail, on the ventral side slightly anterior to the anus. In addition, a few copies of lin-3 mRNA were seen on the ventral side of the animal, slightly behind the posterior gonad arm. We imaged several animals that were slightly older, in the late L3 stage, and observed expression of several copies of lin-3 mRNA in the region where P6.p and its descendants are located (data not shown). We did not consistently detect any lin-3 mRNA in other tissues, although in some animals we observed a single lin-3 mRNA molecule elsewhere (e.g. in or near an intestinal cell).

• Primary Identifier: Expr1150402
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr13451
• Pattern: lin-3p::GFP was strongly expressed in the excretory canal cell, beginning soon after canal cell birth and continuing into early larval development (from ventral enclosure through L1). lin-3p::GFP was also expressed in a variety of other cells further away from the presumptive duct and G1 pore. lin-3p::GFP was strongly expressed in the excretory canal cell, beginning soon after canal cell birth and continuing into early larval development. lin-3p::GFP was also expressed in a variety of other cells further away from the presumptive duct and G1 pore.

• Primary Identifier: Expr2264
• Pattern: This construct was expressed in several tissues: AC, spermatheca and K lineage. In all cases expression could be detected at the appropriate time. In addition, unexpected vulval expression was found from the early to mid fourth larval (L4) stage in the vulF cells, which are the dorsal-most 1 vulval progeny. The expression appeared to be 1-vulva-specific because the vulval lin-3::lacZ expression was absent in animals bearing a strong lin-12(gf) mutation, which confers a multivulva phenotype consisting of only 2 lineages.

• Primary Identifier: Expr15690
• Pattern: In L2 and L3 larvae, mNGr::LIN-3 expression was detected in intracellular punctae and on the basal cortex of the AC. No extracellular mNGr::LIN-3 signal could be detected, suggesting that the majority of mNGr::LIN-3 remains attached to the AC surface after its secretion to the plasma membrane, or that a cleavage product of the mNGr::LIN-3 protein is released from the AC and rapidly taken up by the adjacent VPCs or degraded. The same localization pattern was observed with a multicopy GFP::LIN-3 transgene (zhIs67), in which the GFP tag had been inserted at the same position as in the endogenous mNGr::lin-3(zh112) reporter strain. In wild-type larvae, mNGr::LIN-3 was enriched towards the ventral cortex of the AC from the mid-L2 stage until the mid-L3 stage.

• Primary Identifier: Expr15691
• Pattern: In L2 and L3 larvae, mNGr::LIN-3 expression was detected in intracellular punctae and on the basal cortex of the AC. No extracellular mNGr::LIN-3 signal could be detected, suggesting that the majority of mNGr::LIN-3 remains attached to the AC surface after its secretion to the plasma membrane, or that a cleavage product of the mNGr::LIN-3 protein is released from the AC and rapidly taken up by the adjacent VPCs or degraded. The same localization pattern was observed with a multicopy GFP::LIN-3 transgene (zhIs67), in which the GFP tag had been inserted at the same position as in the endogenous mNGr::lin-3(zh112) reporter strain. In wild-type larvae, mNGr::LIN-3 was enriched towards the ventral cortex of the AC from the mid-L2 stage until the mid-L3 stage.

• Primary Identifier: Expr506
• Remark: Strain injected was lin-3(e1417) unc-22(e66)/++. Transgenic Marker: rol-6(su1006). Construct rescues Vul phenotype. Results confirmed by ablation.
• Pattern: Expressed in Anchor Cell (AC) at L3.

• Primary Identifier: Expr11397
• Remark: Feature : lin-3 enhancer
• Pattern: lin-3 enhancer region, driving anchor cell (AC) specific expression.

• Primary Identifier: Expr2013182
• 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: Expr12789

• Primary Identifier: Expr1028719
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr2031414
• 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).

30 GO Annotation

0 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00002992
• Start: 11054308
• End: 11063768
• Strand: 1

30 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 9461

1 Sequence Ontology Term