scholarly journals Decision letter: Sexually dimorphic control of gene expression in sensory neurons regulates decision-making behavior in C. elegans

2016 ◽  
eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Zoë A Hilbert ◽  
Dennis H Kim

Animal behavior is directed by the integration of sensory information from internal states and the environment. Neuroendocrine regulation of diverse behaviors of Caenorhabditis elegans is under the control of the DAF-7/TGF-β ligand that is secreted from sensory neurons. Here, we show that C. elegans males exhibit an altered, male-specific expression pattern of daf-7 in the ASJ sensory neuron pair with the onset of reproductive maturity, which functions to promote male-specific mate-searching behavior. Molecular genetic analysis of the switch-like regulation of daf-7 expression in the ASJ neuron pair reveals a hierarchy of regulation among multiple inputs—sex, age, nutritional status, and microbial environment—which function in the modulation of behavior. Our results suggest that regulation of gene expression in sensory neurons can function in the integration of a wide array of sensory information and facilitate decision-making behaviors in C. elegans.


2019 ◽  
Author(s):  
Jaeseok Park ◽  
Joshua D Meisel ◽  
Dennis H Kim

AbstractDynamic gene expression in neurons shapes fundamental processes of the nervous systems of animals. But how different stimuli that activate the same neuron can lead to distinct transcriptional responses remains unclear. We have been studying how microbial metabolites modulate gene expression in chemosensory neurons of Caenorhabditis elegans. Considering the diverse environmental stimuli that can activate chemosensory neurons of C. elegans, we have sought to understand how specific transcriptional responses can be generated in these neurons in response to distinct cues. We have focused on the mechanism of rapid (<6 min) and selective transcriptional induction of daf-7, a gene encoding a TGF-β ligand that promotes bacterial lawn avoidance, in the ASJ chemosensory neurons in response to the pathogenic bacterium Pseudomonas aeruginosa. Here, we define the involvement of two distinct cyclic GMP (cGMP)-dependent pathways that are required for daf-7 expression in the ASJ neuron pair in response to P. aeruginosa. We show that a calcium-independent pathway dependent on the cGMP-dependent protein kinase G (PKG) EGL-4, and a canonical calcium-dependent signaling pathway dependent on the activity of a cyclic nucleotide-gated channel subunit CNG-2, function in parallel to activate rapid, selective transcription of daf-7 in response to P. aeruginosa metabolites. Our data suggest a requirement for PKG in promoting the fast, selective early transcription of neuronal genes in shaping responses to distinct microbial stimuli in a pair of chemosensory neurons of C. elegans.Author SummaryThe nervous systems of animals carry out the crucial roles of sensing and interpreting the external environment. When the free-living microscopic roundworm C. elegans is exposed to the pathogenic bacteria Pseudomonas aeruginosa, sensory neurons detect metabolites produced by the pathogen and induce expression of the gene for a neuroendocrine ligand called DAF-7. In turn, activity of DAF-7 is required for the full avoidance response to the P. aeruginosa, allowing the animals to reduce bacterial load and survive longer. Here, we systematically dissect the molecular pathway between the sensation of P. aeruginosa metabolites and the expression of daf-7 in a pair of C. elegans sensory neurons. We show that the intracellular signaling molecule cyclic GMP is a key signaling intermediate. In addition, we show that there are calcium-dependent and calcium-independent pathways that are both required to engage daf-7 expression, highlighting an organizational principle that allows neurons to distinguish between various stimuli.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Lloyd Davis ◽  
Inja Radman ◽  
Angeliki Goutou ◽  
Ailish Tynan ◽  
Kieran Baxter ◽  
...  

Synthetic strategies for optically controlling gene expression may enable the precise spatiotemporal control of genes in any combination of cells that cannot be targeted with specific promoters. We develop an improved genetic code expansion system in C. elegans and use it to create a photo-activatable Cre recombinase. We laser-activate Cre in single neurons within a bilaterally symmetric pair to selectively switch on expression of a loxP controlled optogenetic channel in the targeted neuron. We use the system to dissect, in freely moving animals, the individual contributions of the mechanosensory neurons PLML/PLMR to the C. elegans touch response circuit, revealing distinct and synergistic roles for these neurons. We thus demonstrate how genetic code expansion and optical targeting can be combined to break the symmetry of neuron pairs and dissect behavioural outputs of individual neurons that cannot be genetically targeted.


2021 ◽  
Author(s):  
Adrian Fragoso-Luna ◽  
Cristina Ayuso ◽  
Michael Eibl ◽  
Celia Munoz-Jimenez ◽  
Vladimir Benes ◽  
...  

Control of gene expression in specific tissues and/or at certain stages of development allows the study and manipulation of gene function with high precision. Site-specific genome recombination by the Flippase (FLP) and Cre enzymes has proven particularly relevant. Joint efforts of many research groups have led to the creation of efficient FLP and Cre drivers to regulate gene expression in a variety of tissues in Caenorhabditis elegans. Here, we extend this toolkit by the addition of FLP lines that drive recombination specifically in distal tip cells, the somatic gonad, coelomocytes and the epithelial P lineage. In some cases, recombination-mediated gene knockouts do not completely deplete protein levels due to persistence of long-lived proteins. To overcome this, we developed a spatiotemporally regulated degradation system for GFP fusion proteins (GFPdeg) based on FLP-mediated recombination. Using two stable nuclear pore proteins, MEL-28/ELYS and NPP-2/NUP85 as examples, we report the benefit of combining tissue-specific gene knockout and protein degradation to achieve complete protein depletion. We also demonstrate that FLP-mediated recombination can be utilized to identify nascent transcripts in a tissue of interest. We have adapted thiol(SH)-linked alkylation for the metabolic sequencing of RNA in tissue (SLAM-ITseq) for C. elegans. By focusing on a well-characterized tissue, the hypodermis, we show that the vast majority of genes identified by SLAM-ITseq are known to be expressed in this tissue, but with the added value of temporal resolution. These tools allow combining FLP activity for simultaneous gene inactivation and transcriptomic profiling, thus enabling the inquiry of gene function in various complex biological processes.


Genome ◽  
2010 ◽  
Vol 53 (2) ◽  
pp. 83-102 ◽  
Author(s):  
Hilary Racher ◽  
Dave Hansen

The formation of a fully developed gamete from an undifferentiated germ cell requires progression through numerous developmental stages and cell fate decisions. The precise timing and level of gene expression guides cells through these stages. Translational regulation is highly utilized in the germ line of many species, including Caenorhabditis elegans , to regulate gene expression and ensure the proper formation of gametes. In this review, we discuss some of the developmental stages and cell fate decisions involved in the formation of functional gametes in the C. elegans germ line in which translational control has been implicated. These stages include the mitosis versus meiosis decision, the sperm/oocyte decision, and gamete maturation. We also discuss some of the techniques used to identify mRNA targets; the identification of these targets is necessary to clearly understand the role each RNA-binding protein plays in these decisions. Relatively few mRNA targets have been identified, thus providing a major focus for future research. Finally, we propose some reasons why translational control may be utilized so heavily in the germ line. Given that many species have this substantial reliance on translational regulation for the control of gene expression in the germ line, an understanding of translational regulation in the C. elegans germ line is likely to increase our understanding of gamete formation in general.


2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Shachar Iwanir ◽  
Rotem Ruach ◽  
Eyal Itskovits ◽  
Christian O. Pritz ◽  
Eduard Bokman ◽  
...  

We would like to make our readers aware of the publication by Cohen et al., which reports irrational behaviour in C. elegans olfactory preference[1] . These complementary studies establish C. elegans as a model system to explore the neural mechanisms of decision making.


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