Transforming growth factor (TGF-<font face=symbol>b</font>) regulates normal cell proliferation, differentiation, and survival. In C. elegans, a TGF-<font face=symbol>b</font>-like gene,
daf-7, regulates dauer entry. Mutants for
daf-7 are dauer constitutuve (Daf-c). Many compounds including steroids, other growth factors, and the neurotransmitter serotonin regulate the synthesis and/or the secretion of TGF-<font face=symbol>b</font> in mammals. Serotonin is better known as an important regulator of mood and memory formation, but how it regulates TGF-<font face=symbol>b</font> expression is generally unknown. Transcription of
daf-7 is also regulated by serotonin, since mutants for the serotonin biosynthetic enzyme TPH-1 have severely reduced
daf-7 expression1. Recently it has also been reported that
daf-7 in turn regulates the expression of
tph-12, suggesting a regulatory feedback loop of some kind. I am using transgenic worm lines that express green fluorescent protein (GFP) under the
daf-7 promoter as a tool to understand how
daf-7 transcription is regulated by serotonin. I have measured changes in GFP fluorescence (
daf-7 transcription) caused by mutations in serotonin receptors. Mutations in any one of the known serotonin G-protein coupled receptors, SER-4, SER-1, or SER-7, do not have significant effects on
daf-7::GFP expression in L1 larvae. However, mutations in G<font face=symbol>a</font> proteins, GOA-1 (G<font face=symbol>a</font><sub>o</sub>) and EGL-30 (G<font face=symbol>a</font><sub>q</sub>) significantly reduce
daf-7::GFP expression in the ASI neurons of L1 larvae, and have effects on dauer formation as well. I am currently investigating whether combinations of serotonin receptors mediate the serotonergic regulation of
daf-7 transcription. I am also determining how other signaling genes, important for dauer formation, affect
daf-7 transcription. I am using cell-specific promoters to determine whether the G proteins have a cell autonomous effect on
daf-7 expression, and which serotonergic neurons mediate the effect of TPH-1 on
daf-7 transcription. In addition to looking at the effects of mutations in known serotonin signaling components, I also plan to screen for novel genes that mediate serotonergic regulation of
daf-7 expression. 1 Sze, JY et al (2000) Nature: 560-564. 2 Chang, AJ et al (2006) PLoS Biology:1588-1602. .