Cell fusion is fundamental for reproduction and organ formation. Fusion between most C. elegans epithelial cells is mediated by the EFF-1 fusogen. However, fusion between the anchor cell and the utse syncytium that establishes a continuous uterine-vulval tube proceeds normally in eff-1 mutants. By isolating mutants where the anchor-cell fails to fuse, we identified aff-1. AFF-1 ectopic expression results in fusion of cells that normally do not fuse in C. elegans. The fusogen activity of AFF-1 was further confirmed by its ability to fuse heterologous cells. AFF-1 and EFF-1 differ in their fusogenic activity and expression patterns but share eight conserved predicted disulfide bonds in their ectodomains, including a putative TGF-β-type-I-Receptor domain. We found that FOS-1, the Fos transcription factor ortholog that controls anchor-cell invasion during nematode development, is a specific activator of aff-1-mediated anchor-cell fusion. Thus, FOS-1 links cell invasion and fusion in a developmental cascade.
Bibliographical noteFunding Information:
We thank Y. Kohara for EST clones, A. Fire for vectors, S. Mitani and the NBRP for the aff-1(tm2214) deletion allele, T. Stiernagle and the Caenorhabditis Genetics Center for nematode strains, F. Rey for advice on structural domain interpretation, M. Akerman for bioinformatics advice, and M. Suissa, S. Joshua, K. Brunschwig, D. Cassel, Y. Gruenbaum, E. Schejter, and B-Z Shilo for critically reading the manuscript. This research was supported by grants from the Israel Science Foundation (B.P.) and by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health (L.V.C.).
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology (all)
- Developmental Biology
- Cell Biology