WormMine: Gene WBGene00003029

• WormBase Gene ID: WBGene00003029
• Gene Name: lin-44
• Sequence Name: E01A2.3
• Brief Description: lin-44 encodes one of five C. elegans Wnt signaling ligands; during development, LIN-44 activity is required non-cell-autonomously for polarity specification of asymmetric cell divisions of the B, U, and F cells in the male, and the T cell in males and hermaphrodites; in addition, LIN-44 functions redundantly with MOM-2 and CWN-2 to pattern the P7.p lineage during vulval development; lin-44 expression begins at the 1.5-fold stage of embryogenesis in the posterior hypodermal cells hyp10 and hyp11; during later embryonic stages additional expression in hyp8 and hyp9 is detected; reporter fusions and in situ hybridization studies also reveal weak and inconsistent expression in the anchor cell of the somatic gonad.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable cytokine activity and frizzled binding activity. Involved in several processes, including cell differentiation; nematode male tail tip morphogenesis; and positive regulation of cell projection organization. Predicted to be located in extracellular space. Expressed in several structures, including P6.pa; P6.pp; anchor cell; rectal epithelial cell; and tail. Human ortholog(s) of this gene implicated in several diseases, including Schopf-Schulz-Passarge syndrome; carcinoma (multiple); and split hand-foot malformation 6. Is an ortholog of several human genes including WNT10B (Wnt family member 10B); WNT11 (Wnt family member 11); and WNT9B (Wnt family member 9B).
• Biotype: SO:0001217
• Genetic Position: I :-1.71501 ±0.006592
• Length (nt): 3255

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00003029

Genomics

1 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:E01A2.3.1	E01A2.3.1	1378	I: 4126056-4129310

Other

1 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:E01A2.3	E01A2.3	1047	I: 4126178-4126330

19 RNAi Result

• WBRNAi00068014
• WBRNAi00043557
• WBRNAi00078346
• WBRNAi00003306
• WBRNAi00097725
• WBRNAi00091572
• WBRNAi00027626
• WBRNAi00101705
• WBRNAi00091418
• WBRNAi00101487
• WBRNAi00101907
• WBRNAi00101909
• WBRNAi00101910
• WBRNAi00101690
• WBRNAi00098911
• WBRNAi00101695
• WBRNAi00101344
• WBRNAi00101700
• WBRNAi00101444

49 Allele

• gk962706
• gk963902
• gk964159
• WBVar00240386
• WBVar00243964
• sa490
• gk587820
• gk863113
• gk425424
• gk388915
• gk897139
• gk694067
• gk491849
• gk916849
• gk457523
• gk884323
• gk395056
• gk763612
• gk322832
• gk825614
• gk737520
• gk734081
• gk400895
• gk686994
• gk360814
• gk645594
• WBVar01281488
• WBVar01281490
• WBVar01281489
• gk108634

1 Chromosome

• WormBase ID: I
• Organism: Caenorhabditis elegans
• Length (nt): 15072434

1 Chromosome Location

• Feature . Primary Identifier: WBGene00003029
• Start: 4126056
• End: 4129310
• Strand: 1

4 Data Sets

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

1 Downstream Intergenic Region

• WormBase ID: intergenic_region_chrI_4129311..4129564
• Length (nt): 254
• Chromosome Location: I: 4129311-4129564
• Organism: Caenorhabditis elegans

122 Expression Clusters

Regulated By Treatment	Description	Algorithm	Primary Identifier
	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
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
	Genes that are significantly up regulated in tdp-1(ok803) poly(A) RNA-seq verses in N2.	DESeq v1.14, with cut-off p-value < 0.05 and FDR < 0.1.	WBPaper00046012:tdp-1(ok803)_upregulated
	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 decreased expression in day 3 adult hermaphrodite comparing to in L4 larva glp-1(e2141) animals.	Fold change > 2, FDR < 0.05	WBPaper00064088:Day-3-adult_vs_L4_downregulated_glp-1(e2141)
	Transcripts that showed significantly increased expression in rrf-3(pk1426) comparing to in N2 at embryo stage.	DESeq2v 1.18.1, fold change > 1.5, adjusted p-value < 0.01.	WBPaper00056169:rrf-3(pk1426)_upregulated_embryo
	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 increased expression in aak-1(tm1944);aak-2(ok524) animals comparing to in N2.	DEseq 1.18.0, adjusted p-value < 0.05.	WBPaper00056471:aak-1(tm1944);aak-2(ok524)_upregulated
	Transcripts that showed significantly altered expression after 24 hour exposure to stavudine (d4T) starting at L1 lava stage.	DESeq	WBPaper00053302:stavudine_24h_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 enriched in PHso according to single cell RNAseq.	Genes that pass the Bonferroni threshold for multiple comparisons (q < 0.05) are significantly enriched.	WBPaper00061651:PHso_enriched
	Transcripts that showed significantly decreased expression in dissected female germline comparing to in dissected male germline.	Log2 Fold change > 2 or <-1, p-value < 0.05.	WBPaper00053599:female_vs_male_downregulated
	Transcripts that showed significantly increased expression in oocyte germline cells comparing to in mitosis germline cells.	Log2 Fold change > 2 or <-1, p-value < 0.05.	WBPaper00053599:oocyte_vs_mitosis_upregulated
	Transcripts that showed significantly increased expression in hpk-1(pk1393) comparing to in N2 at adult day 2.	DESeq 2, fold change > 2, FDR < 0.05.	WBPaper00065581:hpk-1(pk1393)_upregulated
	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
	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
	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
	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 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 npr-15(tm12539) comparing to in N2 at L4 larva stage.	Fold change > 2, FDR < 0.05.	WBPaper00066608:npr-15(tm12539)_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 decreased expression after animals were treated with 100uM Psora and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Psora-Allantoin_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Psora from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Psora_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Rapamycin and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Allantoin_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 100uM Rapamycin and 50mM Metformin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rapamycin-Metformin_downregulated
	Transcripts that showed significantly decreased expression after animals were treated with 50uM Rifampicin and 250uM Allantoin from day 1 to day 3 adult hermaphradite.	DESeq2(v1.14.1), fold change > 2, p-value < 0.05	WBPaper00055354:Rifampicin-Allantoin_downregulated
	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 set-2(tm1630) animals at embryo stage, comparing to in N2 animals.	DESeq2 (v2.1.8.3) was used to determine DE genes and to generate principal component and scatter plots. DE genes with FDR < 0.05 were analysed using g:Profiler with Bonferroni correction.	WBPaper00060014:set-2(tm1630)_downregulated

17 Expression Patterns

• Primary Identifier: Expr4953
• Remark: Picture: Figures 2A and 2B.
• Pattern: LIN-44 is secreted by four hypodermal cells in the tail throughout embryonic and larval development.

• Primary Identifier: Expr1031417
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr7984
• Remark: Picture: Figure 2, Figure S1.
• Pattern: Expression of lin-44 was observed only in the tail. Expression was first observed late in embryogenesis. As previously reported, expression was observed in hyp8, hyp9, hpy10 and hyp11. Expression in these cells persisted throughout development. No lin-44 expression was observed in the anchor cell(8/8 lines).

• Primary Identifier: Expr9342
• Pattern: lin-44 was mostly localized to the posterior half of L1 larvae, in a pattern that was already present at the comma stage of embryonic development. lin-44 transcripts were present in the tail hypodermal cells hyp8, hyp9, hyp10 and hyp11, and at later larval stages in the phasmid socket cells PHso1 and PHso2 as previously reported (Herman et al., 1995). In addition, it was found that lin-44 is expressed in the rectal epithelial cells B and Y, demonstrating that lin-44 has a more anterior expression domain than has been observed using reporter transgenes.

• Primary Identifier: Expr3052
• Remark: Reporter gene fusion type not specified.
• Pattern: For lin-44::gfp, as reported previously (See Expr3053), the lin-44 promoter drove expression of GFP in the tail region. Also, faint and inconsistent expression was sometimes observed in the anchor cell. Images of lin-44 expression from the systematic in situ hybridization project are consistent with expression of lin-44 in or near the anchor cell (http:

• Primary Identifier: Expr11635
• Pattern: Plin-44::mCherry is mainly expressed in the tail during the embryonic and adult stages.

• Primary Identifier: Expr14918
• Pattern: lin-44/wnt is expressed in the hypodermal cells at the tail tip region, Interestingly, we noticed that hyp10 often showed the brightest BFP expression among the lin-44-expressing cells at the L2 stage.

• Primary Identifier: Expr3053
• Remark: Repeated and confirmed: lin-44::gfp expression pattern was repeated and confirmed in WBPaper00027140.
• Pattern: Expression was observed only in the tail. The earliest expression was detected in three nuclei at the 1.5-fold stage (approximately 430 min) of embryonic development. The expressing nuclei was hypl0 and hypl1. Later in embryonic development, expression was observed in the other cells of the tail hypodermis, hyp8 and hyp9. In a few animals, simultaneous expression in all the tail hypodermal cells was observed.

• Primary Identifier: Expr3054
• Pattern: The earliest lin-44 transcripts we detected were in the hypl0 and hypll cells at the 1.5-old stage of embryogenesis. Hbridization in the hypl0 and hypll cells was observed through out the rest of embryogenesis. At the 3-fold stage of em- bryogenesis, hybridization was also observed in the other cells of the tail hypodermis, hyp8 and hyp9.

• Primary Identifier: Expr11175
• Pattern: Expression of lin-44 is high throughout the entire life span of the worm and increases during aging. As in development, lin-44 expression was observed only in the posterior of the animal. Expression of lin-44 is present in tail hypodermis, hyp8, hyp9, hyp10, and hyp11 cells. Expression was observed throughout the worm's life span, from day 2 (young) to day 12 (old) of adulthood.

• Primary Identifier: Expr14278
• Pattern: We localized lin-44 by smFISH in C. elegans and saw expression in the sex myoblasts (identified by labeling with hlh-8::GFP (HARFE et al. 1998) and P6.px, and none in the uterus and anchor cell.

• Primary Identifier: Expr2013186
• 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: Expr14919
• Subcellular Localization: The BFP signal was observed on the membrane of the tail hypodermal cells including hyp10, suggesting that NRT::BFP::LIN-44 fusion proteins are localized on the surface of the lin-44-expressing cells.

• Primary Identifier: Expr1018662
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

• Primary Identifier: Expr15697
• 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: Expr2031418
• 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: Expr1147551
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

38 GO Annotation

5 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00003029
• Start: 4126056
• End: 4129310
• Strand: 1

38 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 3255

1 Sequence Ontology Term

• Name: gene

9 Strains

• WBStrain00024027
• WBStrain00027208
• WBStrain00027124
• WBStrain00027149
• WBStrain00007455
• WBStrain00008497
• WBStrain00007444
• WBStrain00007452
• WBStrain00007443

1 Upstream Intergenic Region

• WormBase ID: intergenic_region_chrI_4124765..4126055
• Length (nt): 1291
• Chromosome Location: I: 4124765-4126055
• Organism: Caenorhabditis elegans