Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Shachee Doshi; Emma Price; Justin Landis; Urva Barot; Mariangela Sabatella; Hannes Lans; Robert G. Kalb

doi:10.1016/j.freeradbiomed.2018.12.006

Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Shachee Doshi^*, Emma Price, Justin Landis, Urva Barot, Mariangela Sabatella, Hannes Lans, Robert G. Kalb

^*Corresponding author for this work

Neurology

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Inadequate delivery of oxygen to organisms during development can lead to cell dysfunction/death and life-long disabilities. Although the susceptibility of developing cells to low oxygen conditions changes with maturation, the cellular and molecular pathways that govern responses to low oxygen are incompletely understood. Here we show that developing Caenorhabditis elegans are substantially more sensitive to anoxia than adult animals and that this sensitivity is controlled by nervous system generated hormones (e.g., neuropeptides). A screen of neuropeptide genes identified and validated nlp-40 and its receptor aex-2 as a key regulator of anoxic survival in developing worms. The survival-promoting action of impaired neuropeptide signaling does not rely on five known stress resistance pathways and is specific to anoxic insult. Together, these data highlight a novel cell non-autonomous pathway that regulates the susceptibility of developing organisms to anoxia.

Original language	English (US)
Pages (from-to)	197-208
Number of pages	12
Journal	Free Radical Biology and Medicine
Volume	131
DOIs	https://doi.org/10.1016/j.freeradbiomed.2018.12.006
State	Published - Feb 1 2019

Funding

We thank Dr. Derek Sieburth for valuable strains and resources related to nlp-40 experiments, and Dr. Mei Zhen for strains related to tissue-specific egl-3 rescue experiments. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ), and others were provided by the National BioResource Project , Tokyo Japan. We also thank the Worm Group laboratories at the University of Pennsylvania for their insightful feedback and support, especially Dr. David Raizen for ongoing advice and resource sharing as well as Dr. Matt Nelson for help with designing the ASK-specific nlp-40 rescue construct. We are grateful for the help and support of Kalb laboratory members. This work was funded by National Institutes of Health Grants, NS087077 and NS05225 to R.G.K. H.L. was funded by CancerGenomiCs.nl ( Netherlands Organization for Scientific Research ). M.S. was funded by the ITN ‘aDDRess’ of the European Commission 7th Framework Programme [ 316390 ]. H.L. was funded by CancerGenomiCs.nl (Netherlands Organization for Scientific Research). M.S. was funded by the ITN ‘aDDRess’ of the European Commission 7th Framework Programme [316390].

Keywords

Anoxia
C. elegans
Neuropeptides
egl-3
nlp-40
unc-31

ASJC Scopus subject areas

Physiology (medical)
Biochemistry

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10.1016/j.freeradbiomed.2018.12.006

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title = "Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia",

abstract = "Inadequate delivery of oxygen to organisms during development can lead to cell dysfunction/death and life-long disabilities. Although the susceptibility of developing cells to low oxygen conditions changes with maturation, the cellular and molecular pathways that govern responses to low oxygen are incompletely understood. Here we show that developing Caenorhabditis elegans are substantially more sensitive to anoxia than adult animals and that this sensitivity is controlled by nervous system generated hormones (e.g., neuropeptides). A screen of neuropeptide genes identified and validated nlp-40 and its receptor aex-2 as a key regulator of anoxic survival in developing worms. The survival-promoting action of impaired neuropeptide signaling does not rely on five known stress resistance pathways and is specific to anoxic insult. Together, these data highlight a novel cell non-autonomous pathway that regulates the susceptibility of developing organisms to anoxia.",

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AU - Lans, Hannes

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Neuropeptide signaling regulates the susceptibility of developing C. elegans to anoxia

Abstract

Funding

Keywords

ASJC Scopus subject areas

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