Parallel pathways control C elegans reproductive development in response to environmental cues. Attenuation of
daf-2 insulin-like or
daf-7 TGFbeta-Iike 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
daf9::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.