DFR1 encodes a mesoderm-specific fibroblast growth factor receptor in Drosophila. Here, we identified and characterized a protein-null mutant of DFR1 and examined DFR1 expression in embryos using anti-DFR1 antibody. Mutant phenotypes were completely rescued by a genomic fragment from the DFR1 locus. After invagination, mesodermal cells expressing DFR1 undergo proliferation and spread out dorsally to form a monolayer beneath the ectoderm. In mutant embryos, however, the mesoderm is not capable of extending to the normal dorsal limit and consequently mesodermal cells fail to receive ectodermal signals and thus rendered incapable of differentiating into primordia for the heart, visceral and somatic muscles. DFR1 is also required for normal development of the central nervous system. The absence of DFR1 resulted in the failure of longitudinal glia to enwrap longitudinal axon tracts. DFR1 mutant phenotypes were partially mimicked by the targeted expression of activated Yan, thus demonstrating the MAP kinase pathway to be involved in differentiation of mesoderm.