Identification and characterization of TMEFF2, a novel survival factor forhippocampal and mesencephalic neurons

We have identified a novel mammalian gene, TMEFF2, that encodes a putative transmembrane protein containing two follistatin-like domains and one epide rmal growth factor (EGF)-like domain. The TMEFF2 gene is predominantly expr essed in the brain. In situ hybridization analysis revealed that TMEFF2 is widely expressed in the brain, including hippocampal cornu ammonis, dentate gyrus, and substantia nigra pars compacta. We evaluated the survival effec t of TMEFF2 using primary cultured neurons from several regions of fetal ra t brain following treatment with a recombinant TMEFF2 protein fragment cons isting of the putative extracellular domain. TMEFF2 increased survival of n eurons from the hippocampus and midbrain, but not from the cerebral cortex, indicating that the survival effects of TMEFF2 are specific to certain cel l types. Recombinant TMEFF2 also promoted survival of mesencephalic dopamin ergic neurons. Together, these findings suggest that TMEFF2 may be a novel survival factor for hippocampal and mesencephalic, but not for cortical, ne urons. (C) 2000 Academic Press.