Intercellular signaling of reproductive development by the C. elegans DAF-9 cytochrome P450.
Parallel pathways control C. elegans reproductive development in response to environmental cues. Attenuation of daf-2 insulin-like or daf-7 TGFbeta-like signaling pathways cause developmental arrest at the stress resistant and long-lived dauer stage. Loss-of-function mutations in the cytochrome P450 gene daf-9 also cause dauer arrest and defects in cell migration. A rescuing daf-9::GFP fusion gene driven by the daf-9 promoter is expressed in two head cells at all stages, in the hypodermis from mid-second larval stage (L2) to the fourth larval stage (L4), and in the spermatheca of the adult hermaphrodite. Although the level of daf-9::GFP expression in the head cells and spermatheca is constant, hypodermal daf-9::GFP expression is modulated by multiple inputs. In particular, daf-9::GFP expression in the hypodermis is absolutely dependent on daf-12, the nuclear receptor that is negatively regulated by daf-9 gene activity, suggesting feedback control between daf-9 and daf-12 in this tissue. daf-9 expression exclusively in the hypodermis is sufficient to restore reproductive development in daf-9 mutant animals, suggesting that daf-9 functions in a cell nonautonomous manner. Furthermore, constitutive expression of daf-9 in the hypodermis suppresses dauer arrest of daf-7 mutant animals and inhibits dauer remodelling of some tissues in daf-2 mutant animals. Thus, daf-9 may integrate outputs from daf-2 and daf-7 signaling pathways to relay neuroendocrine signals through synthesis of a lipophilic hormone.
Mak
Ho Yi
HY
Department of Molecular Biology, Massachusetts General Hospital and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Ruvkun
Gary
G
D000375:Aging / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006066:Gonads / Q000254:growth & development; D007814:Larva / Q000254:growth & development; D009154:Mutation; D011401:Promoter Regions, Genetic; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C102095:DAF-7 protein, C elegans; D016212:Transforming Growth Factor beta; D003577:Cytochrome P-450 Enzyme System; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin