LIN-3, a homolog of EGF, is used multiple times as an inductive signal during development of C. elegans. The responses are believed to be mediated through LET-23, a EGFR tyrosine kinase. The outcome of signaling is context-dependent. Reduction of function mutations in both LIN-3 and LET-23 can affect the development of vulva, male tail and posterior ectoderm, cause larval lethality and result in hermaphrodite sterility. We have made a
lin-3::lacZ expression construct which is expressed in several tissues at appropriate times as we expected from previous genetic analysis. In addition, we found unexpected vulval expression from early L4 to mid L4 in the vulF cells, which are the inner most vulval cells. To determine whether this expression could have a functional significance, we examined the expression pattern of let- 23::GFP during the period which corresponds to vulval expression of LIN- 3. We detected expression of LET-23 in the uterine
uv1 cells, the ventral most uterine cells, which suggests possible signaling from the vulva to the uterus. Indeed, our ablation results show that central primary vulva tissue is required and sufficient for the specification of the
uv1 cell fate. When we examined selected LET-23 signaling pathway mutants with a central morphologically normal primary vulva, we found a low to moderate penetrance of
uv1 to utse transformation. EGL-38 is a member of the PAX family of genes, which encode transcription factors implicated in a variety of developmental patterning events.
egl-38(
n578) has defects in the egg-laying system resulting from the absence of
uv1 cells and abnormal vulval patterning. In this genetic background, we found that vulval expression of LIN-3 specifically disappears. let- 23
(sa62), a gain of function mutation of LET-23, is able to suppress the
uv1 defect but not the vulval patterning defect in
egl-38(
n578). These observations suggested that EGL-38 acts upstream of LIN-3 as a positive regulator to regulate the specification of
uv1 cell fate in a cell non- autonomous manner. During normal development of C. elegans, LIN-3 is first produced by the gonadal anchor cell to induce vulval precursor cells to divide and differentiate into vulval tissue. Here we show that LIN-3 signaling from vulval tissue also mediates the specification of
uv1 cell fate. Thus reciprocal EGF signaling coordinates the connection between uterus and vulva.