The dauer larva is a diapause stage formed in response to starvation and overcrowding. Entry into, and exit from, the dauer stage are determined by three environmental cues: dauer-inducing pheromone, food and temperature. Mutations in the
daf-7,
daf-11,
daf-21 and
unc-3 genes result in constitutive dauer larva formation (Daf-c) even with abundant bacterial food. We have shown that
daf-7 encodes a TGF-beta homolog. A
daf-7 promoter::gfp reporter is expressed in a pair of amphidial chemosensory neurons called ASI, whose sensory processes are exposed to the environment. Pheromone inhibits
daf-7 expression and promotes dauer formation (Ren, et al., Science 274:1389, 1996). We have found that
daf-7p::gfp expression is suppressed in
daf-11 and
daf-21 mutants at 25 C and in an
unc-3 null mutant at 27 C. At such temperatures, these mutants form nearly 100 % dauer larvae. DAF-11 is a guanylyl cyclase and UNC-3 is a member of the O/E family of transcription factors, and they are expressed in ASI and other neurons (J. Thomas and T. Starich, pers. comm.). We found that a cGMP analog, 8-Bromo-cGMP, activates
daf-7p::gfp expression in ASI and rescues
daf-11 and
daf-21 Daf-c phenotypes. 8-Bromo-cGMP does not rescue
unc-3 or
daf-11;
unc-3 double mutant Daf-c phenotypes at 27 C, indicating that
unc-3 acts downstream
daf-11. The
daf-7 promoter has a consensus motif recognized by the O/E family members. Deletion of this motif dramatically reduces
daf-7p::gfp expression in ASI neurons at 27 C. Recombinant UNC-3 protein binds to this motif. We propose that in pheromone at 27 C, an unknown G protein-coupled pheromone receptor inhibits DAF-11 guanylyl cyclase and in turn inactivates UNC-3 to turn off
daf-7 transcription in ASI neurons, resulting in dauer formation. Our results provide the first evidence how a TGF-beta like molecule is regulated by a chemosensory cascade in response to environmental cues to control development.