1. Molecular Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA
2. Howard Hughes Medical Institute and Department of Biochemsitry
3. Neuroscience Center and Department of Microbiology
4. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hil, North Carolina 27599, USA
5. Developmental Biology Programme, European Molecular Biology Laboratory, 69117 Heidelberg, Germany
6. Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA
7. Center for Reproductive Biology, Department of Genetics and Cell Biology, Washington State University, Pullman, Washington 99164, USA
8. These authors contributed equally to this work.
9. Present address: Arena Pharmaceuticals, San Diego, California 92121, USA (M.G.).

Correspondence to: Glenn K. Matsushima³ Correspondence and requests for materials should be addressed to G.L. (e-mail: Email: lemke@salk.edu).

We have generated and analysed null mutations in the mouse genes encoding three structurally related receptors with tyrosine kinase activity: Tyro 3, Axl, and Mer^{1, 4}. Mice lacking any single receptor, or any combination of two receptors, are viable and fertile, but male animals that lack all three receptors produce no mature sperm, owing to the progressive death of differentiating germ cells. This degenerative phenotype appears to result from a failure of the tropic support that is normally provided by Sertoli cells of the seminiferous tubules, whose function depends on testosterone and additional factors produced by Leydig cells^{5, 7}. Tyro 3, Axl and Mer are all normally expressed by Sertoli cells during postnatal development, whereas their ligands, Gas6 and protein S, are produced by Leydig cells before sexual maturity, and by both Leydig and Sertoli cells thereafter. Here we show that the concerted activation of Tyro 3, Axl and Mer in Sertoli cells is critical to the role that these cells play as nurturers of developing germ cells. Additional observations indicate that these receptors may also be essential for the tropic maintenance of diverse cell types in the mature nervous, immune and reproductive systems.