A genetic screen for aldicarb resistance of C aenorhabditis elegans dauer larvae uncovers 2 alleles of dach-1, a cytochrome P450 gene

Author:

Son Sangwon1ORCID,Choi Myung-Kyu1ORCID,Lim Daisy S1ORCID,Shim Jaegal2ORCID,Lee Junho1ORCID

Affiliation:

1. Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University , Seoul 08826, Korea

2. Research Institute, National Cancer Center , Goyang 10408, Korea

Abstract

Abstract Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how animal’s sensitivity to drugs that alter synaptic activity is regulated at a specific developmental stage using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated 2 different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the nondauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell nonautonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during the developmental plasticity.

Funder

Samsung Basic Science Foundation

Publisher

Oxford University Press (OUP)

Subject

Genetics (clinical),Genetics,Molecular Biology

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