Reciprocal EGF signaling back to the uterus from the induced C-elegans vulva coordinates morphogenesis of epithelia

Background: Reciprocal signaling between distinct tissues is a general feat ure of organogenesis. Despite the identification of developmental processes in which coordination requires reciprocal signaling, little is known regar ding the underlying molecular details. Here, we use the development of the uterine-vulval connection in the nematode Caenorhabditis elegans as a model system to study reciprocal signaling. Results: In C. elegans, development of the uterine-vulval connection requir es the specification of uterine uv1 cells and morphogenesis of 1 degrees-de rived vulval cells. LIN-3, an epidermal growth factor (EGF) family protein, is first produced by the gonadal anchor cell to induce vulval precursor ce lls to generate vulval tissue. We have shown that lin-3 is also expressed i n the 1 degrees vulval lineage after vulval induction and that the 1 degree s vulva is necessary to induce the uv1 uterine cell fate. Using genetic and cell biological analyses, we found that the specification of uterine uv1 c ells is dependent on EGF signaling from cells of the 1 degrees vulval linea ges to a subset of ventral uterine cells of the gonad. RAS and RAF are nece ssary for this signaling. We also found that EGL-38, a member of the PAX fa mily of proteins, is necessary for transcription of lin-3 in the vulva but not in the anchor cell. A let-23 mutation that confers ligand-independent a ctivity bypasses the requirement for EGL-38 in specification of the uv1 cel l fate. Conclusions: We have shown how relatively simple EGF signals can be used re ciprocally to specify the uterine-vulval connection during C, elegans devel opment. (C) Elsevier Science Ltd ISSN 0960-9822.