The C-terminal binding protein (CTBP-1) regulates dorsal SMD axonal morphology in Caenorhabditis elegans.
- Authors
- Reid, A; Sherry, T J; Yücel, D; Llamosas, E; Nicholas, H R
- Year
- 2015
- Journal
- Neuroscience
- PMID
- 26480814
- DOI
- 10.1016/j.neuroscience.2015.10.026
C-terminal binding proteins (CtBPs) are transcriptional co-repressors which cooperate with a variety of transcription factors to repress gene expression. Caenorhabditis elegans CTBP-1 expression has been observed in the nervous system and hypodermis. In C. elegans, CTBP-1 regulates several processes including Acute Functional Tolerance to ethanol and functions in the nervous system to modulate both lifespan and expression of a lipase gene called lips-7. Incorrect structure and/or function of the nervous system can lead to behavioral changes. Here, we demonstrate reduced exploration behavior in ctbp-1 mutants. Our examination of a subset of neurons involved in regulating locomotion revealed that the axonal morphology of dorsal SMD (SMDD) neurons is altered in ctbp-1 mutants at the fourth larval (L4) stage. Expressing CTBP-1 under the control of the endogenous ctbp-1 promoter rescued both the exploration behavior phenotype and defective SMDD axon structure in ctbp-1 mutants at the L4 stage. Interestingly, the pre-synaptic marker RAB-3 was found to localize to the mispositioned portion of SMDD axons in a ctbp-1 mutant. Further analysis of SMDD axonal morphology at days 1, 3 and 5 of adulthood revealed that the number of ctbp-1 mutants showing an SMDD axonal morphology defect increases in early adulthood and the observed defect appears to be qualitatively more severe. CTBP-1 is prominently expressed in the nervous system with weak expression detected in the hypodermis. Surprisingly, solely expressing CTBP-1a in the nervous system or hypodermis did not restore correct SMDD axonal structure in a ctbp-1 mutant. Our results demonstrate a role for CTBP-1 in exploration behavior and the regulation of SMDD axonal morphology in C. elegans.
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External
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| The regulatory landscape of neurite development in <i>Caenorhabditis elegans</i>. | Godini R et al. | — | 2022 | → |
| The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in <i>Caenorhabditis elegans</i>. | Saul J et al. | — | 2022 | → |
| The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in <i>C. elegans</i> | Saul J et al. | — | 2021 | — |
| Harmonization of L1CAM expression facilitates axon outgrowth and guidance of a motor neuron. | Sherry T et al. | — | 2020 | → |
| Human iPSC-Derived Neuronal Cells From <i>CTBP1</i>-Mutated Patients Reveal Altered Expression of Neurodevelopmental Gene Networks. | Vijayalingam S et al. | — | 2020 | → |
| A sensory-motor neuron type mediates proprioceptive coordination of steering in C. elegans via two TRPC channels. | Yeon J et al. | — | 2018 | → |
| A genome wide association study of fast beta EEG in families of European ancestry. | Meyers JL et al. | — | 2017 | → |