DAF-9, a cytochrome P450 regulating C. elegans larval development and adult longevity.

The daf-9 gene functions to integrate transforming growth factor-beta and insulin-like signaling pathways to regulate Caenorhabditis elegans larval development. Mutations in daf-9 result in transient dauer-like larval arrest, abnormal reproductive development, molting defects and increased adult longevity. The phenotype is sterol-dependent, and dependent on the activity of DAF-12, a nuclear hormone receptor. Genetic tests show that daf-9 is upstream of daf-12 in the genetic pathways for larval development and adult longevity. daf-9 encodes a cytochrome P450 related to those involved in biosynthesis of steroid hormones in mammals. We propose that it specifies a step in the biosynthetic pathway for a DAF-12 ligand, which might be a steroid. The surprising cellular specificity of daf-9 expression (predominantly in two sensory neurons) supports a previously unrecognized role for these cells in neuroendocrine control of larval development, reproduction and life span.

[1]  D L Riddle,et al.  daf-12 encodes a nuclear receptor that regulates the dauer diapause and developmental age in C. elegans. , 2000, Genes & development.

[2]  D. Riddle,et al.  daf-1, a C. elegans gene controlling dauer larva development, encodes a novel receptor protein kinase , 1990, Cell.

[3]  D. Riddle,et al.  A Caenorhabditis elegans type I TGF beta receptor can function in the absence of type II kinase to promote larval development. , 2000, Development.

[4]  Koutarou D. Kimura,et al.  daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. , 1997, Science.

[5]  D L Riddle,et al.  The Caenorhabditis elegans dauer larva: developmental effects of pheromone, food, and temperature. , 1984, Developmental biology.

[6]  M. Patterson,et al.  The Niemann-Pick C1 Protein Resides in a Vesicular Compartment Linked to Retrograde Transport of Multiple Lysosomal Cargo* , 1999, The Journal of Biological Chemistry.

[7]  J. Thomas,et al.  A transmembrane guanylyl cyclase (DAF-11) and Hsp90 (DAF-21) regulate a common set of chemosensory behaviors in caenorhabditis elegans. , 2000, Genetics.

[8]  S. Brenner,et al.  The structure of the nervous system of the nematode Caenorhabditis elegans. , 1986, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[9]  J. Apfeld,et al.  Cell Nonautonomy of C. elegans daf-2 Function in the Regulation of Diapause and Life Span , 1998, Cell.

[10]  Andrew Smith.  Genome sequence of the nematode C-elegans: A platform for investigating biology , 1998 .

[11]  M. Chalfie,et al.  Green fluorescent protein as a marker for gene expression. , 1994, Science.

[12]  A. Sluder,et al.  The nuclear receptor superfamily has undergone extensive proliferation and diversification in nematodes. , 1999, Genome research.

[13]  D. Riddle,et al.  Control of C. elegans Larval Development by Neuronal Expression of a TGF-β Homolog , 1996, Science.

[14]  N. Munakata.  [Genetics of Caenorhabditis elegans]. , 1989, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[15]  G. Ruvkun,et al.  The DAF-3 Smad protein antagonizes TGF-beta-related receptor signaling in the Caenorhabditis elegans dauer pathway. , 1997, Genes & development.

[16]  D. Chitwood.  Biochemistry and function of nematode steroids. , 1999, Critical reviews in biochemistry and molecular biology.

[17]  D. Riddle,et al.  Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans. , 1998, Genetics.

[18]  F. Gonzalez,et al.  Microsomal ethanol oxidizing system: transcriptional and posttranscriptional regulation of cytochrome P450, CYP2E1. , 1991, Alcohol and alcoholism (Oxford, Oxfordshire). Supplement.

[19]  D. Nelson.  Metazoan cytochrome P450 evolution. , 1998, Comparative biochemistry and physiology. Part C, Pharmacology, toxicology & endocrinology.

[20]  C. Kenyon,et al.  daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. , 1997, Science.

[21]  G. Ruvkun,et al.  A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans , 1996, Nature.

[22]  K. Ukena,et al.  Neurosteroid biosynthesis in vertebrate brains. , 1999, Comparative biochemistry and physiology. Part C, Pharmacology, toxicology & endocrinology.

[23]  J. Bessereau,et al.  [C. elegans: of neurons and genes]. , 2003, Medecine sciences : M/S.

[24]  V. Matyash,et al.  Distribution and transport of cholesterol in Caenorhabditis elegans. , 2001, Molecular biology of the cell.

[25]  P. Anderson,et al.  Splicing removes the Caenorhabditis elegans transposon Tc1 from most mutant pre-mRNAs , 1996, Molecular and cellular biology.

[26]  C. Huynh,et al.  A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. , 1992, Genetics.

[27]  Cynthia Kenyon,et al.  Signals from the reproductive system regulate the lifespan of C. elegans , 1999, Nature.

[28]  D. Riddle,et al.  Mutants of Caenorhabditis elegans that form dauer-like larvae. , 1988, Developmental biology.

[29]  B. Lakowski,et al.  The genetics of caloric restriction in Caenorhabditis elegans. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[30]  D. Riddle,et al.  Genetic and Environmental Regulation of Dauer Larva Development -- C. elegans II , 1997 .

[31]  James H. Thomas,et al.  Targets of TGF-β Signaling in Caenorhabditis elegans Dauer Formation , 2000 .

[32]  R. Cassada,et al.  The dauerlarva, a post-embryonic developmental variant of the nematode Caenorhabditis elegans. , 1975, Developmental biology.

[33]  W L Miller,et al.  Molecular biology of steroid hormone synthesis. , 1988, Endocrine reviews.

[34]  M. Basson,et al.  A model for Niemann–Pick type C disease in the nematode Caenorhabditis elegans , 2000, Current Biology.

[35]  Cori Bargmann,et al.  Laser killing of cells in Caenorhabditis elegans. , 1995, Methods in cell biology.

[36]  A. Fleury,et al.  Molecular cloning and expression of guinea pig cytochrome P450c17 cDNA (steroid 17 alpha-hydroxylase/17,20 lyase): tissue distribution, regulation, and substrate specificity of the expressed enzyme. , 1994, DNA and cell biology.

[37]  Michael A. Costa,et al.  Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family. , 2001, Genes & development.

[38]  D. Riddle,et al.  Genes that regulate both development and longevity in Caenorhabditis elegans. , 1995, Genetics.

[39]  C. Kenyon,et al.  A C. elegans mutant that lives twice as long as wild type , 1993, Nature.

[40]  G. Ruvkun,et al.  The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans , 1997, Nature.

[41]  M. Haussler,et al.  Steroid hormone receptors: Evolution, ligands, and molecular basis of biologic function , 1999, Journal of cellular biochemistry.

[42]  B. Lakowski,et al.  Determination of Life-Span in Caenorhabditis elegans by Four Clock Genes , 1996, Science.

[43]  D. Riddle,et al.  A pheromone-induced developmental switch in Caenorhabditis elegans: Temperature-sensitive mutants reveal a wild-type temperature-dependent process. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[44]  M. Klass,et al.  Non-ageing developmental variant of Caenorhabditis elegans , 1976, Nature.

[45]  J. Kaplan,et al.  Synaptic code for sensory modalities revealed by C. elegans GLR-1 glutamate receptor , 1995, Nature.

[46]  Wendy S. Schackwitz,et al.  Chemosensory Neurons Function in Parallel to Mediate a Pheromone Response in C. elegans , 1996, Neuron.

[47]  O. Gotoh,et al.  Divergent structures of Caenorhabditis elegans cytochrome P450 genes suggest the frequent loss and gain of introns during the evolution of nematodes. , 1998, Molecular biology and evolution.

[48]  J. Berg.  Genome sequence of the nematode C. elegans: a platform for investigating biology. , 1998, Science.

[49]  D. Riddle,et al.  The daf-4 gene encodes a bone morphogenetic protein receptor controlling C. elegans dauer larva development , 1993, Nature.

[50]  V. Rottiers,et al.  A hormonal signaling pathway influencing C. elegans metabolism, reproductive development, and life span. , 2001, Developmental cell.

[51]  Koutarou D. Kimura,et al.  Regulation of C. elegans life-span by insulinlike signaling in the nervous system. , 2000, Science.