WormBase Tree Display for Variation: WBVar00091303
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WBVar00091303 | Evidence | Person_evidence | WBPerson499 | ||||||
---|---|---|---|---|---|---|---|---|---|
Name | Public_name | np1 | |||||||
HGVSg | CHROMOSOME_I:g.4569218_4570570delinsAGCGAAC | ||||||||
Sequence_details | SMap | S_parent | Sequence | D1007 | |||||
Flanking_sequences | TAAACTACAGAAGTTCGCTTTTGGA | TACCACATTCACATCAGGACAACTGAAG | |||||||
Mapping_target | D1007 | ||||||||
Type_of_mutation | Insertion | AGTTCGCT | Author_evidence | Mara Andrione | |||||
Deletion | |||||||||
SeqStatus | Sequenced | ||||||||
Variation_type | Allele | ||||||||
Origin | Species | Caenorhabditis elegans | |||||||
Strain | WBStrain00008608 | ||||||||
Laboratory | IB | ||||||||
Status | Live | ||||||||
Affects | Gene | WBGene00000440 | |||||||
Transcript | D1007.1.1 | VEP_consequence | splice_acceptor_variant,splice_donor_variant,coding_sequence_variant,5_prime_UTR_variant,intron_variant | ||||||
VEP_impact | HIGH | ||||||||
cDNA_position | ?-461 | ||||||||
CDS_position | ?-458 | ||||||||
Protein_position | ?-153 | ||||||||
Intron_number | 2-3/4 | ||||||||
Exon_number | 1-4/5 | ||||||||
Interactor | WBInteraction000500657 | ||||||||
WBInteraction000536103 | |||||||||
WBInteraction000536104 | |||||||||
WBInteraction000536105 | |||||||||
WBInteraction000536106 | |||||||||
WBInteraction000536107 | |||||||||
WBInteraction000536108 | |||||||||
WBInteraction000536109 | |||||||||
WBInteraction000536117 | |||||||||
WBInteraction000536118 | |||||||||
WBInteraction000536121 | |||||||||
WBInteraction000536123 | |||||||||
WBInteraction000536125 | |||||||||
WBInteraction000536127 | |||||||||
WBInteraction000536132 | |||||||||
WBInteraction000536135 | |||||||||
WBInteraction000536138 | |||||||||
WBInteraction000536139 | |||||||||
Isolation | Mutagen | UV/TMP | |||||||
Genetics | Interpolated_map_position | I | -1.04587 | ||||||
Mapping_data | In_multi_point | 4204 | |||||||
Description | Phenotype | WBPhenotype:0000134 | Paper_evidence | WBPaper00050371 | |||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | "We evaluated the expression of ten CEH-17 eY1H targets in ceh-17(np1) mutant animals and found that it can both activate and repress gene expression: Four genes are reduced in expression and one is increased (Fig 3G)." Genes with decreased expression: brc-2, vps-39, lsy-13, piga-1. | Paper_evidence | WBPaper00050371 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000135 | Paper_evidence | WBPaper00050371 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | "We evaluated the expression of ten CEH-17 eY1H targets in ceh-17(np1) mutant animals and found that it can both activate and repress gene expression: Four genes are reduced in expression and one is increased (Fig 3G)." Gene with increased expression: srsx-24. | Paper_evidence | WBPaper00050371 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0000795 | Paper_evidence | WBPaper00050847 | |||||||
Curator_confirmed | WBPerson38423 | ||||||||
Remark | "reduced flipping behavior by about half (figure 3D)" | Paper_evidence | WBPaper00050847 | ||||||
Curator_confirmed | WBPerson38423 | ||||||||
Variation_effect | Null | Paper_evidence | WBPaper00050847 | ||||||
Curator_confirmed | WBPerson38423 | ||||||||
Phenotype_assay | Strain | WBStrain00008608 | Paper_evidence | WBPaper00050847 | |||||
Curator_confirmed | WBPerson38423 | ||||||||
Control_strain | WBStrain00000001 | Paper_evidence | WBPaper00050847 | ||||||
Curator_confirmed | WBPerson38423 | ||||||||
WBPhenotype:0000880 | Paper_evidence | WBPaper00056066 | |||||||
Curator_confirmed | WBPerson18979 | ||||||||
Remark | ALA axon undeveloped | Paper_evidence | WBPaper00056066 | ||||||
Curator_confirmed | WBPerson18979 | ||||||||
Penetrance | Incomplete | Paper_evidence | WBPaper00056066 | ||||||
Curator_confirmed | WBPerson18979 | ||||||||
Recessive | Paper_evidence | WBPaper00056066 | |||||||
Curator_confirmed | WBPerson18979 | ||||||||
Variation_effect | Probable_null_via_phenotype | Paper_evidence | WBPaper00056066 | ||||||
Curator_confirmed | WBPerson18979 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00056066 | ||||
Curator_confirmed | WBPerson18979 | ||||||||
GO_term | GO:0030424 | PATO:0001483 | Paper_evidence | WBPaper00056066 | |||||
Curator_confirmed | WBPerson18979 | ||||||||
WBPhenotype:0000882 | Paper_evidence | WBPaper00056066 | |||||||
Curator_confirmed | WBPerson18979 | ||||||||
Remark | PVD 1° dendrite branch short | Paper_evidence | WBPaper00056066 | ||||||
Curator_confirmed | WBPerson18979 | ||||||||
Penetrance | Incomplete | Paper_evidence | WBPaper00056066 | ||||||
Curator_confirmed | WBPerson18979 | ||||||||
Recessive | Paper_evidence | WBPaper00056066 | |||||||
Curator_confirmed | WBPerson18979 | ||||||||
Variation_effect | Probable_null_via_phenotype | Paper_evidence | WBPaper00056066 | ||||||
Curator_confirmed | WBPerson18979 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0006831 | PATO:0000460 | Paper_evidence | WBPaper00056066 | ||||
Curator_confirmed | WBPerson18979 | ||||||||
GO_term | GO:0044307 | PATO:0000574 | Paper_evidence | WBPaper00056066 | |||||
Curator_confirmed | WBPerson18979 | ||||||||
WBPhenotype:0001224 | Paper_evidence | WBPaper00036308 | |||||||
WBPaper00004283 | |||||||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPerson499 | |||||||||
Remark | "We then scored the extent of ALA axon migration and found that the ceh-10(rf) animals showed a ceh-17-like truncation of the ALA axons, albeit less severe (Fig 6B,C). While the ceh-17(lf) axon migration phenotype is similar when scored in either L1 or L2 stage animals, we found that a greater fraction of ceh-10(rf) ALA axons reach the tail by the L2 stage than at L1. This was surprising, as wild-type ALA axons complete their migration before hatching (Pujol et_al, 2000)." | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
The two ALA axons normally run along the lateral cord all the way to the tail (Fig. 3A), stopping beyond the anus in the adult. In the mutant, ALA was present and its axons initially followed their normal trajectory, but they stopped prematurely (Fig. 3B). This stalling phenotype was highly penetrant (Fig. 3D), with 100% of ALA axons shorter than in wild type and 76% stopping close to the gonad primordium, between the DA4 and DA6 motor neuronal commissures. In a few cases (5%), the axons not only stopped before the gonad but then backtracked along the lateral cord (Fig. 3C). | Paper_evidence | WBPaper00004283 | |||||||
Curator_confirmed | WBPerson499 | ||||||||
In a mutant ceh-17 background, a dramatic shortening was observed, with more than 60% of SIA axons stopping next to the gonad primordium (Fig. 3E). In addition, some of the axons grew anteriorly to the nerve ring, which was never observed in wildtype worms (data not shown). | Paper_evidence | WBPaper00004283 | |||||||
Curator_confirmed | WBPerson499 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00036308 | ||||
WBPaper00004283 | |||||||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPerson499 | |||||||||
WBbt:0005361 | PATO:0000460 | Paper_evidence | WBPaper00004283 | ||||||
Curator_confirmed | WBPerson499 | ||||||||
GO_term | GO:0030424 | PATO:0000460 | Paper_evidence | WBPaper00004283 | |||||
Curator_confirmed | WBPerson499 | ||||||||
PATO:0002364 | Paper_evidence | WBPaper00004283 | |||||||
Curator_confirmed | WBPerson499 | ||||||||
Phenotype_assay | Genotype | unc-53:GFP | Paper_evidence | WBPaper00036308 | |||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPhenotype:0001278 | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
Remark | "In wild type, a let-23:LET-23-GFP translational reporter is expressed in several non-neuronal cells and a small number of neurons, including ALA (Van Buskirk and Sternberg, 2007). We examined the expression of this reporter in ceh-17(np1) null mutant animals and found its expression to be severely decreased in ALA, with other sites of expression intact (Fig 1A, Table 2)." | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
"Phospholipase C-γ (PLC-γ, encoded by plc-3), a direct target of activated EGFR, is required for ALA-dependent sleep (Van Buskirk and Sternberg, 2007). We examined the expression of a PLC-γ transcriptional reporter that is normally expressed in ALA at all stages and detectable in a small number of other neurons (S. Xu, personal communication). We found plc-3 expression to be specifically disrupted in ALA in the ceh-17(np1) animals (Fig 1A,B)." (see also Table 2) | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
The ceh-17(np1) null mutant exhibits decreased expression of the ver-3::GFP transgene in the ALA neuron (Table 2) | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
The ceh-17(np1) null mutant exhibits decreased expression of the ida-1::GFP transgene in the ALA neuron (Table 2, Figure 3) | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
The ceh-17(np1) null mutant exhibits decreased expression of the flp-7::GFP transgene in the ALA neuron (Table 2, Figure 3) | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
"We analyzed the expression of a GFP reporter driven by this same ceh-14 promoter fragment (ceh-14:GFP; kindly provided by I. Hope), and found that its expression was specifically decreased in ALA in the ceh-17(np1) mutant (Fig 2A). The defect could not be detected by eye, but quantification of fluorescence revealed a significant decrease in ALA-specific expression across larval stages." | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
"In ceh-17(np1) mutants, ceh-17:GFP expression in ALA becomes compromised as development proceeds (Fig 2D). This temporal profile argues against cross-regulatory interactions with CEH-14 being the predominant contributor to the observed CEH-17 autoregulation, as the cross-regulatory effects are consistent across larval stages (Fig 2A,B)." | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
"We analyzed the expression of des-2:GFP in the ALA neuron of ceh-14 and ceh-17 null mutant animals and found that at the L1 stage, reporter expression is dependent on CEH-14 but not on CEH-17 (Fig 4B), consistent with our observed genetic results with deg-3(gf). At the L4 stage, however, deg-3 expression is dependent on both factors (Fig 4B,C), revealing different temporal requirements for CEH-17 and CEH-14 in deg-3 expression." | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00036308 | ||||
Curator_confirmed | WBPerson2987 | ||||||||
Phenotype_assay | Genotype | let-23:LET-23-GFP | Paper_evidence | WBPaper00036308 | |||||
Curator_confirmed | WBPerson2987 | ||||||||
plc-3::YFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
ver-3::GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
ida-1::GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
flp-7::GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
ceh-14::GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
ceh-17::GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
des-2:GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPhenotype:0001524 | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
Remark | 100% of ceh-17(np1) animals were resistant to EGF-induced sleep (Table 1); "We found that similar to ceh-17 animals, the ALA neuron is present and its cell body is positioned normally (Fig 1A, DIC images) but the ceh-14(ch3) null mutant animals are completely resistant to the behavioral effects of EGF expression (Table 1)... Our observation that CEH-17 is dispensable for deg-3 expression early in development led us to examine whether this might be true for multiple CEH-17 targets. If so, the ceh-17 null mutation might confer a lower level of EGF-resistance during early larval stages than in adults. We therefore assayed L2 stage animals for EGFinduced sleep, and found that, in contrast to ceh-14 mutants, the EGF-resistance of ceh-17 mutants is significantly lower at the L2 stage than in adults (Table 3)." | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
Penetrance | Complete | 100 | Paper_evidence | WBPaper00036308 | |||||
Curator_confirmed | WBPerson2987 | ||||||||
Phenotype_assay | Treatment | Animals carrying the hs:LIN-3 transgene were well fed and grown at 20C. Young adult animals were scored 2 hours after heat shock for EGF-induced sleep behavior (see Materials and methods). | Paper_evidence | WBPaper00036308 | |||||
Curator_confirmed | WBPerson2987 | ||||||||
Genotype | hs:LIN-3 | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPhenotype:0002432 | Paper_evidence | WBPaper00057148 | |||||||
WBPaper00059734 | |||||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | Reduction of ALA neuron function impairs all forms of SIS. | Paper_evidence | WBPaper00059734 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00059734 | ||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0002433 | Paper_evidence | WBPaper00050011 | |||||||
Curator_confirmed | WBPerson712 | ||||||||
Remark | Resistance to pumping quiescence after heatshock in flp-13 mutants was much weaker than the negative controls, ceh-14 and ceh-17, suggesting that flp-13 is not the only neuropeptide necessary for pumping quiescence during stress-induced sleep (flp-13: 79% 3% pumping quiescent compared to ceh-14: 0% 0% and compared to ceh-17: 5% 3%; p < 0.001; Figure 2A). The ceh-14 and ceh-17 mutants, previously shown to bestrongly resistant to heat shock [7, 14], displayed locomotionquiescence after heat shock (ceh-14: 0% 0% locomotionquiescent before heat shock compared to ceh-14: 36% 4%locomotion quiescent after heat shock; ceh-17: 0% 0% locomotionquiescent before heat shock compared to ceh-17:56% 5% locomotion quiescent after heat shock; p < 0.01;Figure 2B). | Paper_evidence | WBPaper00050011 | ||||||
Curator_confirmed | WBPerson712 | ||||||||
WBPhenotype:0002490 | Paper_evidence | WBPaper00004283 | |||||||
Curator_confirmed | WBPerson499 | ||||||||
Remark | In a mutant ceh-17 background, a dramatic shortening was observed, with more than 60% of SIA axons stopping next to the gonad primordium (Fig. 3E). In addition, some of the axons grew anteriorly to the nerve ring, which was never observed in wildtype worms (data not shown). | Paper_evidence | WBPaper00004283 | ||||||
Curator_confirmed | WBPerson499 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0005361 | PATO:0000460 | Paper_evidence | WBPaper00004283 | ||||
Curator_confirmed | WBPerson499 | ||||||||
GO_term | GO:0030424 | PATO:0000628 | Paper_evidence | WBPaper00004283 | |||||
Curator_confirmed | WBPerson499 | ||||||||
Phenotype_not_observed | WBPhenotype:0000306 | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
Remark | The ceh-17(np1) null mutant exhibits no change in expression of the unc-119::YFP transgene in the ALA neuron (Table 2) | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
The ceh-17(np1) null mutant exhibits no change in expression of the rab-3::GFP transgene in the ALA neuron (Table 2) | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
"To determine whether CEH-10 and CEH-14 also play roles in ALA axon migration, we examined unc-53:GFP (pNP21; N. Pujol), which labels several neurons including ALA and the DA neurons of the ventral cord that extend commissural axons, marking body length (Stringham et al., 2002). In wild-type animals this reporter labels the ALA axons during the L1-L2 stages. We first examined unc-53:GFP in ALA in ceh-17(null) and ceh-10(rf) L1-L2 animals and found that expression of the reporter was not detectably impaired (Fig 6A)." | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00036308 | ||||
Curator_confirmed | WBPerson2987 | ||||||||
Phenotype_assay | Genotype | unc-119::YFP | Paper_evidence | WBPaper00036308 | |||||
Curator_confirmed | WBPerson2987 | ||||||||
rab-3::GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
unc-53:GFP | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPhenotype:0000424 | Paper_evidence | WBPaper00004283 | |||||||
Curator_confirmed | WBPerson499 | ||||||||
Remark | a FRMFamide-like reactivity is normally detected in ALA (Schinkmann and Li, 1992) and the vesicular acetylcholine transporter (VAChT) encoded by unc-17 (Alfonso et al., 1993) is expressed in SIAs (J. Duerr, personal communication). Expression of these markers was unaffected in ceh-17 mutants (see Materials and Methods and data not shown). | Paper_evidence | WBPaper00004283 | ||||||
Curator_confirmed | WBPerson499 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00004283 | ||||
Curator_confirmed | WBPerson499 | ||||||||
WBbt:0005361 | PATO:0000460 | Paper_evidence | WBPaper00004283 | ||||||
Curator_confirmed | WBPerson499 | ||||||||
WBPhenotype:0001310 | Paper_evidence | WBPaper00036308 | |||||||
Curator_confirmed | WBPerson2987 | ||||||||
Remark | "We found that similar to ceh-17 animals, the ALA neuron is present and its cell body is positioned normally (Fig 1A, DIC images) but the ceh-14(ch3) null mutant animals are completely resistant to the behavioral effects of EGF expression (Table 1)." | Paper_evidence | WBPaper00036308 | ||||||
Curator_confirmed | WBPerson2987 | ||||||||
EQ_annotations | Anatomy_term | WBbt:0003955 | PATO:0000460 | Paper_evidence | WBPaper00036308 | ||||
Curator_confirmed | WBPerson2987 | ||||||||
WBPhenotype:0001765 | Paper_evidence | WBPaper00031936 | |||||||
Curator_confirmed | WBPerson2021 | ||||||||
Remark | Mutants respond normally to CO2 | Paper_evidence | WBPaper00031936 | ||||||
Curator_confirmed | WBPerson2021 | ||||||||
EQ_annotations | Life_stage | WBls:0000057 | PATO:0000460 | Paper_evidence | WBPaper00031936 | ||||
Curator_confirmed | WBPerson2021 | ||||||||
Phenotype_assay | Treatment | 10% CO2 | Paper_evidence | WBPaper00031936 | |||||
Curator_confirmed | WBPerson2021 | ||||||||
Reference | WBPaper00031936 | ||||||||
WBPaper00004283 | |||||||||
WBPaper00036308 | |||||||||
WBPaper00050011 | |||||||||
WBPaper00050371 | |||||||||
WBPaper00050847 | |||||||||
WBPaper00056066 | |||||||||
WBPaper00057148 | |||||||||
WBPaper00059734 | |||||||||
WBPaper00064927 | |||||||||
Remark | Updated the context of this variation to reflect a reported Insertion of 8bp at the deletion site in the ZIM lab isolate. | Author_evidence | Mara Andrione | ||||||
Curator_confirmed | WBPerson1983 | ||||||||
Method | Deletion_and_insertion_allele |