WormMine: Gene WBGene00001475

• WormBase Gene ID: WBGene00001475
• Gene Name: fmi-1
• Sequence Name: F15B9.7
• Brief Description: fmi-1 encodes a highly conserved cadherin-like protein with unique domain composition of six EGF and two laminin G domains, a GPS cleavage site and seven-pass transmembrane domain; fmi-1 plays a crucial role in pioneer axon navigation as well as pioneer-mediated follower navigation; FMI-1 is required cell autonomously in pioneer and partially non-cell autonomously in the follower; different domains of FMI-1 are required for pioneer and follower navigation; mutations in fmi-1 cause strong axon navigation defects of VNC pioneer axons; HSN axons are more susceptible to changes in fmi-1 protein; LIN-17/frizzled functions together with fmi-1 in follower axon navigation; in addition, FMI-1 functions together with the CDH-4 cadherin to regulate GABAergic neuronal development; FMI-1 is expressed in neurons and localized to pioneer and follower axons during and after nervous system development; in the embryos FMI-1::GFP is found in axons in the nerve ring, the tail and along the dendrites of sensory neurons.
• Organism: Caenorhabditis elegans
• Automated Description: Predicted to enable G protein-coupled receptor activity and calcium ion binding activity. Involved in anterior/posterior axon guidance and interneuron axon guidance. Located in axon. Expressed in nervous system and somatic nervous system. Human ortholog(s) of this gene implicated in hereditary lymphedema. Is an ortholog of human CELSR2 (cadherin EGF LAG seven-pass G-type receptor 2).
• Biotype: SO:0001217
• Genetic Position: V :4.81313 ±0.003033
• Length (nt): 14341

1 Organism

• Name: Caenorhabditis elegans
• Taxon Id: 6239

1 Synonyms

• Value: WBGene00001475

Genomics

3 Transcripts

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
Transcript:F15B9.7a.1	F15B9.7a.1	8070	V: 13019061-13033401
Transcript:F15B9.7b.1	F15B9.7b.1	6714	V: 13022913-13033149
Transcript:F15B9.7c.1	F15B9.7c.1	4749	V: 13026193-13033149

Other

3 CDSs

WormMine ID	Sequence Name	Length (nt)	Chromosome Location
CDS:F15B9.7b	F15B9.7b	6714	V: 13022913-13023379
CDS:F15B9.7a	F15B9.7a	7791	V: 13019088-13019593
CDS:F15B9.7c	F15B9.7c	4749	V: 13026193-13026506

6 RNAi Result

• WBRNAi00066947
• WBRNAi00001265
• WBRNAi00044701
• WBRNAi00000627
• WBRNAi00013361
• WBRNAi00101845

194 Allele

• gk963271
• gk963301
• gk964458
• gk964459
• WBVar02061653
• WBVar02061654
• WBVar02061655
• gk326583
• gk250801
• ttTi13425
• ttTi13422
• gk250802
• gk840268
• ttTi13426
• WBVar01868839
• WBVar01868835
• WBVar01868836
• WBVar01868837
• WBVar01868838
• WBVar01868842
• WBVar01868843
• WBVar01868844
• WBVar01868845
• WBVar01868840
• WBVar01868841
• WBVar01868846
• WBVar01868847
• WBVar01868828
• WBVar01868829
• WBVar01868827

1 Chromosome

• WormBase ID: V
• Organism: Caenorhabditis elegans
• Length (nt): 20924180

1 Chromosome Location

• Feature . Primary Identifier: WBGene00001475
• Start: 13019061
• End: 13033401
• 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_chrV_13033402..13033522
• Length (nt): 121
• Chromosome Location: V: 13033402-13033522
• Organism: Caenorhabditis elegans

291 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 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
	Genes significantly enriched (> 2x, FDR < 5%) in a particular cell-type versus a reference sample of all cells at the same stage.	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:A-class-motor-neurons_larva_enriched
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
	Neuronally enriched transcripts according to a comparison of neuronal nuclei IP samples to total nuclei using isolation of nuclei from tagged specific cell types (INTACT) technology.	DESEQ2, fold change > 2 and FDR < 0.01.	WBPaper00062103:neuron_enriched
	Genes that showed increased expression in wdr-5(ok1417) comparing with in N2.	Statistical analysis for misexpression was performed using a moderated t test from the package limma. All genes with a false discovery rate (FDR) of <= 5% (p <= 0.05) were selected as differentially regulated.	WBPaper00045861:wdr-5(ok1417)_upregulated
Bacteria infection: Enterococcus faecalis	Genes with increased expression after 24 hours of infection by E.faecalis Fold changes shown are pathogen vs OP50.	For RNA-seq and tiling arrays, log2 fold changes between gene expression values of infected versus uninfected nematodes were calculated. For log2 fold changes > 0.00001 the values > 81.25th percentile were defined as up-regulated and for log2 fold changes < -0.00001 the values < 18.75th percentile were defined as down-regulated.	WBPaper00038438:E.faecalis_24hr_upregulated_TilingArray
	Transcripts that showed significantly increased 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_upregulated
	Transcripts that showed significantly increased 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_upregulated
	Transcripts that showed significantly increased 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_upregulated
	Transcripts that showed significantly increased 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_upregulated
	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
	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 expressed in hypodermis, according to PAT-Seq analysis using Pdpy-7-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:hypodermis_expressed
	Transcripts expressed in NMDA neuron, according to PAT-Seq analysis using Pnmr-1-GFP-3XFLAG mRNA tagging.	Cufflinks FPKM value >=1.	WBPaper00050990:NMDA-neuron_expressed
	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 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 increased expression in alg-1(gk214), comparing to in N2.	DESeq2, Fold change > 1.5.	WBPaper00051404:alg-1(gk214)_upregulated
	Genes that showed significantly increased expression in daf-2(e1370);hel-1(gk148684) comparing to in hel-1(gk148684)	To identify DEGs, Students t test and the log2 median ratio test were performed to compute t values and median ratios for all the annotated genes. The adjusted P values from each test were computed using an empirical distribution of the null hypothesis, which was obtained from random permutations of the samples. Finally, the adjusted P values from the individual tests were combined to compute the overall P values using Stouffers method , and genes with overall P < 0.05 and fold change > 1.5 were selected as DEGs.	WBPaper00047131:daf-2(e1370)_upregulated_hel-1(gk148684)-background
	Transcripts depleted in purified oocyte P bodies comparing to in the whole animal.	DESeq2, FDR < 0.05, fold change > 2.	WBPaper00065975:P-body_vs_WholeAnimal_depleted
	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 increased expression in sftb-1(cer6) deletion homozygous comparing to to in N2 animals at L4 larva stage.	DESeq2, fold change > 2	WBPaper00058725:sftb-1(cer6)_downregulated
Pheromone	Pheromone-induced transcripts that showed significantly decreased expression in post dauer animals comparing to wild type control.	edgeR	WBPaper00053713:Pheromone-induced_postdauer_vs_control_downregulated
Starvation	Starvation-induced transcripts that showed significantly increased expression in post dauer animals comparing to wild type control.	edgeR	WBPaper00053713:Starvation-induced_postdauer_vs_control_upregulated
	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:A-class-motor-neurons_L2-larva_expressed

13 Expression Patterns

• Primary Identifier: Expr1030879
• Pattern: Tiling arrays expression graphs

• Primary Identifier: Expr9138
• Remark: Picture: Fig 4.
• Subcellular Localization: FMI-1::GFP localized diffusely to major axon tracts such as the nerve ring and the ventral cord. In the embryo, during stages of axon outgrowth, FMI-1::GFP was found in axons in the nerve ring, the tail and along dendrites of sensory neurons.

• Primary Identifier: Expr15186
• Pattern: Consistent with prior reports (Huarcaya Najarro and Ackley, 2013; Steimel et al., 2010), we found that fmi-1 was expressed throughout the C. elegans nervous system at all stages of development, revealed by a high-dose translational FMI-1::GFP reporter that contains the 2615 bp fmi-1 promoter and the genomic fmi-1 sequence injected at 30 ng/ul of DNA concentration (twnEx458). FMI-1::GFP was enriched in the nerve ring and the ventral nerve cord, highlighting the role of FMI-1 in axon and synapse development. We would like to note that these findings do not exclude low level of fmi-1 expression in non-neural tissues that is below the detection threshold of our transgene.

• Primary Identifier: Expr10008
• Pattern: Consistent colocalization of GFP and RFP was observed between Pfmi-1-gfp and Pacr-2-rfp in the DA, VA, and VB and weakly in the DB cholinergic neurons. We occasionally observed a limited coexpression of Punc-25- rfp and Pfmi-1-gfp in the DDs of some L1 animals (<10%), but never in the VDs (>L2).
• Subcellular Localization: FMI-1 accumulated to a region of neuropil around the nerve ring and the ventral cord. FMI-1 was also present in the dorsal cord in young animals but was rarely observed in neuronal cell bodies. In wild-type animals, FMI-1 was concentrated in the nervous system but did not overlap with a marker of synaptic vesicles (SNT-1). Thus, our data suggest that FMI-1 is primarily present in nonsynaptic regions of the ventral cord. However, because of the en passant organization of synapses formed in the ventral nerve cord, it is not possible to determine where FMI-1 is localized with single axon/synapse resolution.

• Primary Identifier: Expr10751
• Pattern: FMI-1::GFP was detected in the VNC in early L1s, and was therefore present prior to the birth of the VD neurons (not shown). At early L2 stage, when VD neurons are forming their anterior neurites, the FMI-1 protein was consistently present along the VNC. It was also present in a punctate pattern along the membrane in the cell bodies of the PVP pioneer and PVQ follower neurons and the cholinergic neurons (not shown). fmi-1 expression was not observed in the VD neurons (n=25 animals).

• Primary Identifier: Expr2011855
• 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: Expr9136
• Remark: Picture: Fig 4.
• Pattern: GFP expression could first be observed in the embryo during gastrulation in neuronal precursors. At the comma and 1.5-fold stage, expression was apparent in neurons in the head, the tail and along the ventral cord. Expression was maintained into the adult stage. Using cell type-specific markers, expression of the fmi-1p construct was confirmed in many neurons, including PVP and PVQ. HSN neurons started to express fmi-1 post-embryonically before axon outgrowth and maintained expression in adults.

• Primary Identifier: Expr9137
• Remark: Picture: Fig 4.
• Pattern: Differences in the expression pattern between the this construct and the one used in Expr9136 were minor. However, expression in SDQ, PVD and PDE neurons was seen only with the fmi-1pintron construct, suggesting that additional elements controlling expression are located in introns.

• Primary Identifier: Expr13510
• Pattern: FMI-1-GFP localized to the nerve ring bundle of 1.5-fold wild-type embryos.

• Primary Identifier: Expr2030093
• 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: Expr15187
• Subcellular Localization: FMI-1::GFP showed membrane enrichment in the cell body of PVD. Punctate FMI-1::GFP could also be found in the 1 dendrites and occasionally in the 2 or 3 dendrites. The low signal-to-noise ratio of FMI-1::GFP in peripheral PVD branches precluded verification of possible FMI-1 localization to the tips of growing 3 dendrites.

• Primary Identifier: Expr1148674
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/hashimshony2015

• Primary Identifier: Expr1025182
• Pattern: Developmental gene expression time-course. Raw data can be downloaded from ftp://caltech.wormbase.org/pub/wormbase/datasets-published/levin2012

17 GO Annotation

11 Homologues

1 Locations

• Feature . Primary Identifier: WBGene00001475
• Start: 13019061
• End: 13033401
• Strand: 1

17 Ontology Annotations

0 Regulates Expr Cluster

1 Sequence

• Length: 14341

1 Sequence Ontology Term