The C-terminal binding protein (CTBP-1) regulates dorsal SMD axonal morphology in Caenorhabditis elegans

Reid, Anna; Sherry, Tessa; Yücel, Duygu; Llamosas, Estelle; Nicholas, Hannah R.

doi:10.1016/j.neuroscience.2015.10.026

Cited by 10 publications

(17 citation statements)

References 49 publications

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“…We further dissected their relative contributions of the dorsal and ventral SMD neurons by expressing the trp-1 cDNA or trp-2 cDNA specifically in the SMDD and/or SMDV neurons under the control of the glr-1 p -Δ 1 and flp-7 promoters, respectively. The glr-1 p -Δ 1 promoter drives transgene expression in SMDD and some ventral nerve cord neurons but not in SMDV neurons; the flp-7 promoter drives expression consistently in several neurons, including SMDV but also weakly and occasionally in SMDD ( S8B Fig ) [ 38 , 39 ]. Interestingly, glr-1 p -Δ 1 promoter–driven expression of either TRP-1 or TRP-2 fully rescued the ventral circling phenotype of the trp-1 trp-2 double mutants, but flp-7 promoter–driven expression produced a weaker rescue ( Fig 1G , S8A Fig ).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, ablation of the SMDV neurons induces dorsal circling locomotion ( Fig 4B and 4C ). Because ctbp-1 mutants show defects in the neuronal processes of SMDD but not SMDV neurons [ 39 ], we examined the locomotion of ctbp-1 mutants. C-terminal binding protein 1 (CTBP-1) is a transcriptional repressor of C-terminal binding protein, which regulates neuronal development [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…Because ctbp-1 mutants show defects in the neuronal processes of SMDD but not SMDV neurons [ 39 ], we examined the locomotion of ctbp-1 mutants. C-terminal binding protein 1 (CTBP-1) is a transcriptional repressor of C-terminal binding protein, which regulates neuronal development [ 39 ]. We found that ctbp-1 ( ok498 ) mutant animals exhibited the ventral circling phenotype like the trp-1 trp-2 double mutants ( Fig 4D ).…”

Section: Resultsmentioning

confidence: 99%

“…A 2.6-kb fragment of the trp-1 promoter and a 2.9-kb fragment of the trp-2 promoter from the start codon were amplified by PCR and inserted into the pPD95.77 vector. For the rescue experiments, glr-1 p- Δ 1 (for SMDD; a gift from Hannah Nicholas) [ 39 ], flp-7 p (for SMDV) [ 38 ], flp-22 p -Δ 4 (for SMDD/V), and twk-16 p (for DVA; a gift from Shawn Xu) [ 13 ] were fused with a trp-1 cDNA, a trp-2 cDNA, a trp-4 cDNA (gift from Shawn Xu) [ 36 ], and a trpγ cDNA (a gift from Craig Montell) [ 8 ]. The trp-1 cDNA and the trp-2 cDNA were amplified by PCR from a cDNA library.…”

Section: Methodsmentioning

confidence: 99%

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A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels

Yeon

Kim

et al. 2018

PLoS Biol

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Animal locomotion is mediated by a sensory system referred to as proprioception. Defects in the proprioceptive coordination of locomotion result in uncontrolled and inefficient movements. However, the molecular mechanisms underlying proprioception are not fully understood. Here, we identify two transient receptor potential cation (TRPC) channels, trp-1 and trp-2, as necessary and sufficient for proprioceptive responses in C. elegans head steering locomotion. Both channels are expressed in the SMDD neurons, which are required and sufficient for head bending, and mediate coordinated head steering by sensing mechanical stretches due to the contraction of head muscle and orchestrating dorsal head muscle contractions. Moreover, the SMDD neurons play dual roles to sense muscle stretch as well as to control muscle contractions. These results demonstrate that distinct locomotion patterns require dynamic and homeostatic modulation of feedback signals between neurons and muscles.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels

Yeon

Kim

et al. 2018

PLoS Biol

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“…In addition, an early GWAS of alcohol and nicotine dependence reported an association of CTBP2 and DSM-IV Alcohol Dependence in an Australian cohort of 1,224 cases and 1,162 controls, although the association did not meet genome-wide significant criteria ( p -value: 3.91×10 −7 ;(Lind et al, 2010)). Further support for the role of CTBP2 in alcohol related behavior comes from model organism work (Grotewiel and Bettinger, 2015); a genetic screen in nematode Caenorhabditis elegans identifies ctbp-1 (the ortholog of CTBP2 ) as a key regulator required for the development of acute functional tolerance to ethanol (Bettinger et al, 2012; Reid et al, 2015). While this previous literature lends corroborating support for the association of CTBP2 and AUD reported here, this finding should clearly be replicated in independent, larger samples.…”

Section: Discussionmentioning

confidence: 99%

A genome wide association study of fast beta EEG in families of European ancestry

Meyers

Zhang

Manz

et al. 2017

International Journal of Psychophysiology

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BACKGROUND Differences in fast beta (20–28 Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2). METHOD In a sample of 1,564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings. RESULTS Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5×10−8). The most significant SNP was rs2252790 (p<2.6×10−8; MAF= 0.36; β= 0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p= 1.2×10−6) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3×10−4; β= 0.29). Previous studies have indicated that DSE is involved in a network of genes integral to membrane organization; gene-based tests indicated that several variants within this network (i.e., DSE, ZEB2, RND3, MCTP1, and CTBP2) were also associated with beta EEG (empirical p<0.05), and of these genes, ZEB2 and CTBP2 were associated with DSM-V Alcohol Use Disorder (AUD; empirical p<0.05). DISCUSSION In this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples.

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Development of a Nervous System with Increasing Complexity in Lower Eukaryotic Animals

Malla

Amajala

Neelapu

et al. 2021

Developmental Biology in Prokaryotes and Lower Eukaryotes

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The C-terminal binding protein (CTBP-1) regulates dorsal SMD axonal morphology in Caenorhabditis elegans

Cited by 10 publications

References 49 publications

A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels

A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels

A genome wide association study of fast beta EEG in families of European ancestry

Development of a Nervous System with Increasing Complexity in Lower Eukaryotic Animals

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