Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans

Meng, Lingfeng; Zhang, Albert; Jin, Yishi; Yan, Dong

doi:10.7554/elife.19510

Cited by 25 publications

(15 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MDL-28170 inhibits both cathepsin B and calpain cysteine proteases, although only the former were downregulated in high-quality daf-2(RNAi) oocytes (Figure 2A). To distinguish between these classes of proteases, we also evaluated the effects of a calpain-specific inhibitor, PD-150606 [26]; we found that this calpain inhibitor did not significantly affect oocyte morphology maintenance (Figure 3E), suggesting that cathepsin B inhibition is responsible for the improved oocyte quality we observed upon MDL-28170 treatment.…”

Section: Resultsmentioning

confidence: 99%

“…For cathepsin B and/or calpain inhibition experiments, wild-type hermaphrodites were exposed to MDL-28170, PD-150606, or the DMSO control as either mated day 1 adults or, in the delayed treatment experiments, as mated day 3 adults. Individually plated mated hermaphrodites were exposed to a final concentration of 20 μM MDL-28170 (Sigma-Aldrich, St. Louis, MO, USA) [25], 20 μM PD-150606 (Sigma-Aldrich) [26], or Dimethylsulfoxide (DMSO; ATCC: The Global Bioresearch Center, Manassas, Virginia, USA) as the control. MDL-28170 and PD-150606 were both dissolved in DMSO to a concentration of 65.4 mM, and immediately before use, each stock mixture (or the same volume of DMSO alone) was diluted in water to 0.04 mM; 100 μL was spread over each 4 mL NGM plate, and plates were seeded with OP50 E. coli after the liquid had dried.…”

Section: Star Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Insulin Signaling Regulates Oocyte Quality Maintenance with Age via Cathepsin B Activity

et al. 2018

View full text Add to dashboard Cite

A decline in female reproduction is one of the earliest hallmarks of aging in many animals, including invertebrates and mammals [1-4]. The insulin/insulin-like growth factor-1 signaling (IIS) pathway has a conserved role in regulating longevity [5] and also controls reproductive aging [2, 6]. Although IIS transcriptional targets that regulate somatic aging have been characterized [7, 8], it was not known whether the same mechanisms influence reproductive aging. We previously showed that Caenorhabditis elegans daf-2 IIS receptor mutants extend reproductive span by maintaining oocyte quality with age [6], but IIS targets in oocytes had not been identified. Here, we compared the transcriptomes of aged daf-2(-) and wild-type oocytes, and distinguished IIS targets in oocytes from soma-specific targets. Remarkably, IIS appears to regulate reproductive and somatic aging through largely distinct mechanisms, although the binding motif for longevity factor PQM-1 [8] was also overrepresented in oocyte targets. Reduction of oocyte-specific IIS targets decreased reproductive span extension and oocyte viability of daf-2(-) worms, and pqm-1 is required for daf-2(-)'s long reproductive span. Cathepsin-B-like gene expression and activity levels were reduced in aged daf-2(-) oocytes, and RNAi against cathepsin-B-like W07B8.4 improved oocyte quality maintenance and extended reproductive span. Importantly, adult-only pharmacological inhibition of cathepsin B proteases reduced age-dependent deterioration in oocyte quality, even when treatment was initiated in mid-reproduction. This suggests that it is possible to pharmacologically slow age-related reproductive decline through mid-life intervention. Oocyte-specific IIS target genes thereby revealed potential therapeutic targets for maintaining reproductive health with age.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Star Methodsmentioning

confidence: 99%

Insulin Signaling Regulates Oocyte Quality Maintenance with Age via Cathepsin B Activity

et al. 2018

View full text Add to dashboard Cite

show abstract

“…elegans [55]. Nevertheless, integration of neurons with glial cells can be carried out by molecules released by one cell type binding membrane receptors of other cell type as reported by many authors (e.g.…”

Section: Discussionmentioning

confidence: 93%

Oligodendrocytes Remodel the Genomic Fabrics of Functional Pathways in Astrocytes

Iacobaş¹,

Iacobaş²,

Stout³

et al. 2020

Preprint

View full text Add to dashboard Cite

We profiled the transcriptomes of primary mouse cortical astrocytes cultured alone or co-cultured with immortalized precursor oligodendrocytes. The experimental set-up (insert systems) prevented formation of gap junction channels but allowed free exchange of the two culture media. The study complements our previously published reports that the genomic fabrics of major functional pathways in oligodendrocytes are substantially remodeled by the proximity of non-touching astrocytes. Here, we present new analysis indicating that the transcriptomic landscape of astrocytes likewise changes significantly in the proximity of non-touching oligodendrocytes. The research was stimulated by the reported transcriptomic similarity between the brains of Cx43KO and Cx32KO mice, both substantially different from that of the Cx36KO mice. Since the three connexins are expressed in different cell types (Cx43 in astrocytes, Cx32 in oligodendrocytes and Cx36 in neurons), altogether these findings support the idea of a “panglial transcriptomic syncytium” in the mouse brain. Going further, our results suggest that integration in a heterocellular tissue modulates not only the expression profile but also the expression control and networking of the genes in each cell phenotype.

show abstract

“…In another forward genetic screen for genes regulating synapse position of GABAergic RME neurons, a gap junctional role of UNC-7 was found to be critical for both SV and active zone localization ( Meng et al, 2016 ) ( Fig. 2 C).…”

Section: Innexins Have Many Roles In the Nervous Systemmentioning

confidence: 99%

Gap junctions: historical discoveries and new findings in the C aenorhabditis elegans nervous system

et al. 2020

Self Cite

View full text Add to dashboard Cite

Gap junctions are evolutionarily conserved structures at close membrane contacts between two cells. In the nervous system, they mediate rapid, often bi-directional, transmission of signals through channels called innexins in invertebrates and connexins in vertebrates. Connectomic studies from Caenorhabditis elegans have uncovered a vast number of gap junctions present in the nervous system and non-neuronal tissues. The genome also has 25 innexin genes that are expressed in spatial and temporal dynamic pattern. Recent findings have begun to reveal novel roles of innexins in the regulation of multiple processes during formation and function of neural circuits both in normal conditions and under stress. Here, we highlight the diverse roles of gap junctions and innexins in the C. elegans nervous system. These findings contribute to fundamental understanding of gap junctions in all animals.

show abstract

Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans

Cited by 25 publications

References 74 publications

Insulin Signaling Regulates Oocyte Quality Maintenance with Age via Cathepsin B Activity

Insulin Signaling Regulates Oocyte Quality Maintenance with Age via Cathepsin B Activity

Oligodendrocytes Remodel the Genomic Fabrics of Functional Pathways in Astrocytes

Gap junctions: historical discoveries and new findings in the C aenorhabditis elegans nervous system

Contact Info

Product

Resources

About