TY - JOUR
T1 - Hormonal control of C. elegans dauer formation and life span by a Rieske-like oxygenase
AU - Rottiers, Veerle
AU - Motola, Daniel L.
AU - Gerisch, Birgit
AU - Cummins, Carolyn L.
AU - Nishiwaki, Kiyoji
AU - Mangelsdorf, David J.
AU - Antebi, Adam
N1 - Funding Information:
The authors would like to thank J.H. Thomas for the nrc-1 and ncr-2 strains, the CGC for other nematode strains, Y. Kohara for cDNAs, the Sanger Center for cosmid clones, and A. Fire for GFP vectors. We would also like to thank S. Pletcher and members of the Antebi lab for critical reading of the manuscript, and R. Niwa and H. Kataoka for communicating unpublished results. This work was supported by Baylor College of Medicine Seed Fund (A.A.), NIH (A.A., D.J.M.), NIH/NURSA (A.A., D.J.M.), European Union (A.A.), Max Planck Gesellschaft (A.A., B.G., V.R.), Glenn/AFAR BIG Award (A.A.), the Howard Hughes Medical Institute (D.J.M., C.L.C.), and the Robert A. Welch Foundation (D.J.M.).
PY - 2006/4
Y1 - 2006/4
N2 - C. elegans diapause, gonadal outgrowth, and life span are regulated by a lipophilic hormone, which serves as a ligand to the nuclear hormone receptor DAF-12. A key step in hormone production is catalyzed by the CYP450 DAF-9, but the extent of the biosynthetic pathway is unknown. Here, we identify a conserved Rieske-like oxygenase, DAF-36, as a component in hormone metabolism. Mutants display larval developmental and adult aging phenotypes, as well as patterns of epistasis similar to that of daf-9. Larval phenotypes are potently reversed by crude lipid extracts, 7-dehydrocholesterol, and a recently identified DAF-12 sterol ligand, suggesting that DAF-36 works early in the hormone biosynthetic pathway. DAF-36 is expressed primarily within the intestine, a major organ of metabolic and endocrine control, distinct from DAF-9. These results imply that C. elegans hormone production has multiple steps and is distributed, and that it may provide one way that tissues register their current physiological state during organismal commitments.
AB - C. elegans diapause, gonadal outgrowth, and life span are regulated by a lipophilic hormone, which serves as a ligand to the nuclear hormone receptor DAF-12. A key step in hormone production is catalyzed by the CYP450 DAF-9, but the extent of the biosynthetic pathway is unknown. Here, we identify a conserved Rieske-like oxygenase, DAF-36, as a component in hormone metabolism. Mutants display larval developmental and adult aging phenotypes, as well as patterns of epistasis similar to that of daf-9. Larval phenotypes are potently reversed by crude lipid extracts, 7-dehydrocholesterol, and a recently identified DAF-12 sterol ligand, suggesting that DAF-36 works early in the hormone biosynthetic pathway. DAF-36 is expressed primarily within the intestine, a major organ of metabolic and endocrine control, distinct from DAF-9. These results imply that C. elegans hormone production has multiple steps and is distributed, and that it may provide one way that tissues register their current physiological state during organismal commitments.
KW - Devbio
KW - Signaling
UR - http://www.scopus.com/inward/record.url?scp=33645527191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645527191&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2006.02.008
DO - 10.1016/j.devcel.2006.02.008
M3 - Article
C2 - 16563875
AN - SCOPUS:33645527191
SN - 1534-5807
VL - 10
SP - 473
EP - 482
JO - Developmental cell
JF - Developmental cell
IS - 4
ER -