UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in <i>C. elegans</i>

Stetina, Stephen E. Von; Fox, Rebecca; Watkins, Kathie L.; Starich, Todd A; Shaw, Joseph W.; Miller, David M.

doi:10.1101/gad.1502107

Cited by 56 publications

(100 citation statements)

References 43 publications

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“…Ectopic expression of ceh-12 in unc-4 mutants is limited to posterior VA motor neurons and VA input specificity in this location depends on ceh-12. These findings suggest that UNC-4 might regulate multiple targets that function in parallel to specify inputs to selected VA motor neurons in different ventral cord domains (Von Stetina et al, 2007b). Here, we report the discovery that ceh-12 expression in posterior VA motor neurons is activated by a specific Wnt protein, EGL-20, that is secreted from adjacent cells in this region.…”

Section: Introductionmentioning

confidence: 70%

“…3). We have shown that one of these VB proteins, the HB9 (MNX1) homolog CEH-12, is sufficient to rewire VA motor neurons with VB-type inputs (Von Stetina et al, 2007b). Thus, these findings revealed a regulatory switch in which differential expression RESEARCH ARTICLE Wnt pathways control synaptic choice of the transcription factors, UNC-4 versus CEH-12, in VAs results in alternate sets of presynaptic inputs.…”

Section: Introductionmentioning

confidence: 91%

“…In all cases, the experimenter was blind to genotype to avoid bias. Fisher's Exact Test was used to calculate a P-value for statistical significance (Fisher, 1925 Stetina et al, 2007b). ceh-12 is ectopically expressed in posterior VAs in unc-4 mutants and is specifically required for the mis-wiring of VAs in this region (Von Stetina et al, 2007b).…”

Section: Discussionmentioning

confidence: 99%

“…A movement assay ('tapping assay') detected effects of specific mutants on backward locomotion (Von Stetina et al, 2007b). For each genotype, n>50 L4-young adults were tapped on the head with a platinum wire.…”

Section: Movement Assaymentioning

confidence: 99%

“…AVB gap junctions in the ventral cord were detected by anti-GFP immunostaining in L4 larvae and specific motor neurons were identified as described (Von Stetina et al, 2007b). n≥10 for each neuron.…”

Section: Detecting Avb Gap Junctions With Ventral Cord Motor Neuronsmentioning

confidence: 99%

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UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit

et al. 2012

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SUMMARYCoordinated movement depends on the creation of synapses between specific neurons in the motor circuit. In C. elegans, this important decision is regulated by the UNC-4 homeodomain protein. unc-4 mutants are unable to execute backward locomotion because VA motor neurons are mis-wired with inputs normally reserved for their VB sisters. We have proposed that UNC-4 functions in VAs to block expression of VB genes. This model is substantiated by the finding that ectopic expression of the VB gene ceh-12 (encoding a homolog of the homeodomain protein HB9) in unc-4 mutants results in the mis-wiring of posterior VA motor neurons with VB-like connections. Here, we show that VA expression of CEH-12 depends on a nearby source of the Wnt protein EGL-20. Our results indicate that UNC-4 prevents VAs from responding to a local EGL-20 cue by disabling a canonical Wnt signaling cascade involving the Frizzled receptors MIG-1 and MOM-5. CEH-12 expression in VA motor neurons is also opposed by a separate pathway that includes the Wnt ligand LIN-44. This work has revealed a transcriptional mechanism for modulating the sensitivity of specific neurons to diffusible Wnt ligands and thereby defines distinct patterns of synaptic connectivity. The existence of comparable Wnt gradients in the vertebrate spinal cord could reflect similar roles for Wnt signaling in vertebrate motor circuit assembly.

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Section: Introductionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Movement Assaymentioning

confidence: 99%

Section: Detecting Avb Gap Junctions With Ventral Cord Motor Neuronsmentioning

confidence: 99%

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UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit

et al. 2012

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Antagonistic regulation of homeologous uncx.L and uncx.S genes orchestrates myotome and sclerotome differentiation in the evolutionarily divergent vertebral column of Xenopus laevis

Sánchez,

Lazarte,

Abdala

et al. 2023

J Exp Zool Pt B

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In anurans, the vertebral column diverges widely from that of other tetrapods; yet the molecular mechanisms underlying its morphogenesis remain largely unexplored. In this study, we investigate the role of the homeologous uncx.L and uncx.S genes in the vertebral column morphogenesis of the allotetraploid frog Xenopus laevis. We initiated our study by cloning the uncx orthologous genes in the anuran Xenopus and determining their spatial expression patterns using in situ hybridization. Additionally, we employed gain‐of‐function and loss‐of‐function approaches through dexamethasone‐inducible uncx constructs and antisense morpholino oligonucleotides, respectively. Comparative analysis of the messenger RNA sequences of homeologous uncx genes revealed that the uncx.L variant lacks the eh1‐like repressor domain. Our spatial expression analysis indicated that in the presomitic mesoderm and somites, the transcripts of uncx.L and uncx.S are located in overlapping domains. Alterations in the function of uncx genes significantly impact the development and differentiation of the sclerotome and myotome, resulting in axial skeleton malformations. Our findings suggest a scenario where the homeologous genes uncx.L and uncx.S exhibit antagonistic functions during somitogenesis. Specifically, uncx.S appears to be crucial for sclerotome development and differentiation, while uncx.L primarily influences myotome development. Postallotetraploidization, the uncx.L gene in X. laevis evolved to lose its eh1‐like repressor domain, transforming into a “native dominant negative” variant that potentially competes with uncx.S for the same target genes. Finally, the histological analysis revealed that uncx.S expression is necessary for the correct formation of pedicles and neural arch of the vertebrae, and uncx.L is required for trunk muscle development.

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Freedom of expression: cell‐type‐specific gene profiling

Otsuki

Cheetham

Brand

2014

WIREs Developmental Biology

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Cell fate and behavior are results of differential gene regulation, making techniques to profile gene expression in specific cell types highly desirable. Many methods now enable investigation at the DNA, RNA and protein level. This review introduces the most recent and popular techniques, and discusses key issues influencing the choice between these such as ease, cost and applicability of information gained. Interdisciplinary collaborations will no doubt contribute further advances, including not just in single cell type but single-cell expression profiling.

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UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans

Cited by 56 publications

References 43 publications

UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit

UNC-4 antagonizes Wnt signaling to regulate synaptic choice in the C. elegans motor circuit

Antagonistic regulation of homeologous uncx.L and uncx.S genes orchestrates myotome and sclerotome differentiation in the evolutionarily divergent vertebral column of Xenopus laevis

Freedom of expression: cell‐type‐specific gene profiling

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