Chemical genetics identifies c-Src as an activator of primitive ectoderm formation in murine embryonic stem cells.
Multiple Src family kinases (SFKs) are present in murine embryonic stem (mES) cells. Whereas complete inhibition of SFK activity blocks mES cell differentiation, sole inhibition of the SFK member c-Yes induces differentiation. Thus, individual SFKs may have opposing roles in the regulation of mES cell fate. To test this possibility, we generated SFK mutants with engineered resistance to a nonselective SFK inhibitor. The presence of an inhibitor-resistant c-Src mutant, but not analogous mutants of Hck, Lck, c-Yes, or Fyn, reversed the differentiation block associated with inhibitor treatment, resulting in the formation of cells with properties of primitive ectoderm. These results show that distinct SFK signaling pathways regulate mES cell fate and demonstrate that the formation of primitive ectoderm is regulated by the activity of c-Src.
Meyn
Malcolm A
MA
University of Pittsburgh School of Medicine, Department of Microbiology and Molecular Genetics, Pittsburgh, PA 15213-2536, USA. mam71@pitt.edu
Smithgall
Thomas E
TE
D000818:Animals; D002384:Catalysis; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D004475:Ectoderm / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology*; D005821:Genetic Techniques; D051379:Mice; D008956:Models, Chemical; D008968:Molecular Conformation; D009154:Mutation; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology; D019061:src-Family Kinases / Q000378:metabolism*
D019061:src-Family Kinases