The cytochrome P450 DAF-9 plays a central role in the choice between continuous reproductive growth or arrest at the third stage dauer diapause. Sensory cues, including food, temperature, and pheromone initially regulate production of TGF-beta and insulin-like endocrine factors, which somehow converge on DAF-9. In favorable environments, DAF-9 likely produces a lipophilic hormone, possibly a steroid, for the nuclear hormone receptor DAF-12, which promotes reproductive growth. In unfavorable environments, hormone production is suppressed, and DAF-12 selects diapause. Consistent with an endocrine function,
daf-9::gfp is expressed in a few tissues--a pair of head neurons, the hypodermis, and the spermatheca--which mediate developmental decisions for the whole organism. We became interested in the regulation and tissue specific functions of
daf-9. Interestingly, only hypodermal expression is dramatically regulated by environmental and genetic inputs. Under reproductive growth conditions, expression is low. Weak dauer inducing conditions result in compensatory upregulation, whereas strong dauer inducing conditions shut off hypodermal expression altogether. Similarly conditional Daf-c mutants,
daf-7/TGF-beta or
daf-2/insulin-like receptor, strongly express hypodermal
daf-9 at a semi-permissive temperature (20 degrees ), but downregulate expression at the non-permissive temperature (25 degrees ). Surprisingly, hypodermal
daf-9 regulation is strictly
daf-12(+) dependent, suggesting that
daf-9 is feedback regulated by
daf-12. We propose that
daf-9 regulation reflects a homeostatic mechanism to mediate the all-or-none choice between reproductive growth and diapause. To see whether hypodermal
daf-9 is instructive for diapause or simply a readout of the pathway, we constitutively expressed
daf-9 exclusively in the hypodermis. This expression efficiently rescue the Daf-c and Mig phenotypes of
daf-9 mutants. By contrast, neuronal
daf-9 expression gives partial rescue. Moreover hypodermal
daf-9 expression also rescues the Daf-c phenotype of
daf-2 and
daf-7 animals, suggesting that
daf-9 "hormone replacement therapy" can overcome the defects of suppressed insulin and TGF-beta signaling. Currently, we are performing ageing expreiments to see if there is tissue specific regulation for this process as well. Consistent with its proposed role in hormone production, these results show that
daf-9 acts cell non-autonomously to regulate diapause, that hypodermal
daf-9 is a central point of regulation by environmental and genetic inputs, and that hypodermal
daf-9 is sufficient to drive reproductive growth.