Signaling by the worm FGF receptor, EGL-15, is attenuated by the action of the CLR-1 receptor tyrosine phosphatase. Mutations that compromise the activity of CLR-1 result in hyperactive FGF signaling, leading to a dramatic Clr phenotype characterized by the accumulation of clear fluid within the pseudocoelomic space. Animals that completely lose EGL-15 function arrest early in larval development. To understand how FGFR signaling controls fluid balance in C. elegans, we sought to determine the cellular basis of these phenotypic defects.To investigate the cellular site of EGL-15 action, we analyzed the expression pattern of EGL-15 using several approaches. Immunofluorescence studies of EGL-15 indicate that EGL-15 is expressed in hypodermal cells as well as the sex myoblasts, type I vulval muscles, and some neurons (S.J. Goodman and I. Sasson, unpublished data). The importance of hypodermal expression was highlighted by the identification of a hypodermal enhancer element within the
egl-15 promoter. A deletion analysis of the
egl-15 promoter identified a 200bp sequence (
e15) that is essential for full-scale
egl-15 promoter activity. An artificial promoter containing two copies of this enhancer fused to a minimal
pes-10 promoter (Pe15*2) is able to drive
egl-15 rescue activity. Therefore, this
e15 element is both necessary and sufficient for complete
egl-15 promoter activity. A Pe15*2::GFP reporter is expressed mainly in hypodermal cells, suggesting that an important site of EGL-15 function is in hypodermal cells. The importance of hypodermal expression is supported by mutant rescue assays that use tissue-specific promoters to drive either CLR-1 or EGL-15 expression. The same subset of promoters that can restore
egl-15 rescue can also restore
clr-1 rescue, suggesting that EGL-15 and CLR-1 act in the same tissue to regulate fluid balance. This site is likely to be the hypodermis since promoters that drive expression in hypodermal cells (Pdpy-7 and Prol-6) can drive full
clr-1 and
egl-15 rescue activity, while a body wall muscle promoter (Punc-54) cannot. Interestingly, a mosaic analysis of
let-756, the gene encoding the FGF responsible for the essential function of EGL-15, suggests that LET-756 is also required in the hypodermis. The requirement for both the ligand and the receptor in the hypodermis suggests an autocrine model for FGF signaling to regulate fluid flux in worms.