Publications by authors named "Jakob Gramstrup Petersen"

5 Publications

  • Page 1 of 1

Control of Neuropeptide Expression by Parallel Activity-dependent Pathways in Caenorhabditis elegans.

Sci Rep 2017 01 31;7:38734. Epub 2017 Jan 31.

Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia.

Monitoring of neuronal activity within circuits facilitates integrated responses and rapid changes in behavior. We have identified a system in Caenorhabditis elegans where neuropeptide expression is dependent on the ability of the BAG neurons to sense carbon dioxide. In C. elegans, CO sensing is predominantly coordinated by the BAG-expressed receptor-type guanylate cyclase GCY-9. GCY-9 binding to CO causes accumulation of cyclic GMP and opening of the cGMP-gated TAX-2/TAX-4 cation channels; provoking an integrated downstream cascade that enables C. elegans to avoid high CO. Here we show that cGMP regulation by GCY-9 and the PDE-1 phosphodiesterase controls BAG expression of a FMRFamide-related neuropeptide FLP-19 reporter (flp-19::GFP). This regulation is specific for CO-sensing function of the BAG neurons, as loss of oxygen sensing function does not affect flp-19::GFP expression. We also found that expression of flp-19::GFP is controlled in parallel to GCY-9 by the activity-dependent transcription factor CREB (CRH-1) and the cAMP-dependent protein kinase (KIN-2) signaling pathway. We therefore show that two parallel pathways regulate neuropeptide gene expression in the BAG sensory neurons: the ability to sense changes in carbon dioxide and CREB transcription factor. Such regulation may be required in particular environmental conditions to enable sophisticated behavioral decisions to be performed.
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http://dx.doi.org/10.1038/srep38734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282578PMC
January 2017

A novel role for the zinc-finger transcription factor EGL-46 in the differentiation of gas-sensing neurons in Caenorhabditis elegans.

Genetics 2015 Jan 12;199(1):157-63. Epub 2014 Nov 12.

Biotech Research and Innovation Centre, University of Copenhagen, 2200 Copenhagen N, Denmark

Oxygen (O2) and carbon dioxide (CO2) provoke distinct olfactory behaviors via specialized sensory neurons across metazoa. In the nematode C. elegans, the BAG sensory neurons are specialized to sense changes in both O2 and CO2 levels in the environment. The precise functionality of these neurons is specified by the coexpression of a membrane-bound receptor-type guanylyl cyclase GCY-9 that is required for responses to CO2 upshifts and the soluble guanylyl cyclases GCY-31 and GCY-33 that mediate responses to downshifts in O2. Expression of these gas-sensing molecules in the BAG neurons is partially, although not completely, controlled by ETS-5, an ETS-domain-containing transcription factor, and EGL-13, a Sox transcription factor. We report here the identification of EGL-46, a zinc-finger transcription factor, which regulates BAG gas-sensing fate in partially parallel pathways to ETS-5 and EGL-13. Thereby, three conserved transcription factors collaborate to ensure neuron type-specific identity features of the BAG gas-sensing neurons.
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http://dx.doi.org/10.1534/genetics.114.172049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4286680PMC
January 2015

Neuronal cell fate decisions:  O2 and CO2 sensing neurons require egl-13/Sox5.

Worm 2013 Oct 25;2(4):e27284. Epub 2013 Nov 25.

Biotech Research and Innovation Centre; University of Copenhagen; Ole Maaløes Vej 5; Copenhagen, Denmark.

We recently conducted a study that aimed to describe the differentiation mechanisms used to generate O2 and CO2 sensing neurons in C. elegans. We identified egl-13/Sox5 to be required for the differentiation of both O2 and CO2 sensing neurons. We found that egl-13 functions cell autonomously to drive O2 and CO2 sensing neuron fate and is therefore essential for O2 and CO2 sensing-induced behaviors. Through systematic dissection of the egl-13 promoter we identified upstream regulators of egl-13 and proposed a model of how differentiation of O2 and CO2 sensing neurons is regulated. In this commentary we discuss our findings and open questions we wish to address in future studies.
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http://dx.doi.org/10.4161/worm.27284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3988123PMC
October 2013

EGL-13/SoxD specifies distinct O2 and CO2 sensory neuron fates in Caenorhabditis elegans.

PLoS Genet 2013 May 9;9(5):e1003511. Epub 2013 May 9.

Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark.

Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2) and carbon dioxide (CO2). In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral responses to exquisite changes in O2 or CO2 levels via different sensory receptors. How the diversification of the O2- and CO2-sensing neurons is established is poorly understood. We show here that the molecular identity of both the BAG (O2/CO2-sensing) and the URX (O2-sensing) neurons is controlled by the phylogenetically conserved SoxD transcription factor homolog EGL-13. egl-13 mutant animals fail to fully express the distinct terminal gene batteries of the BAG and URX neurons and, as such, are unable to mount behavioral responses to changes in O2 and CO2. We found that the expression of egl-13 is regulated in the BAG and URX neurons by two conserved transcription factors-ETS-5(Ets factor) in the BAG neurons and AHR-1(bHLH factor) in the URX neurons. In addition, we found that EGL-13 acts in partially parallel pathways with both ETS-5 and AHR-1 to direct BAG and URX neuronal fate respectively. Finally, we found that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms of neuronal diversification and the regulation of molecular factors that may be conserved in higher organisms.
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http://dx.doi.org/10.1371/journal.pgen.1003511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650002PMC
May 2013

A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity.

PLoS One 2012 29;7(3):e34014. Epub 2012 Mar 29.

The Helen L. and Martin S. Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, Molecular Neurobiology Program, New York, New York, United States of America.

Many animals possess neurons specialized for the detection of carbon dioxide (CO(2)), which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2) is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2). The ETS-5 transcription factor is necessary for the specification of CO(2)-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO(2)-detection and transforms neurons into CO(2)-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2)-sensing neurons in other phyla.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0034014PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315506PMC
November 2012
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