Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin-1-induced activation of STAT3

Cardiotrophin-1 (CT-1) belongs to the interleukin (IL-)6 family of cytokine s that share membrane glycoprotein 130 (gp130) as a receptor component crit ical for signal transduction, We here observed that CT-1 was expressed in m ouse fetal neuroepithelial cells, and was capable of inducing astrocyte dif ferentiation from these cells in a synergistic manner with bone morphogenet ic protein (BMP)-2, whose expression was also found in the fetal brain. CT- 1-induced astrocyte differentiation was solely gp130-dependent. CT-1-stimul ation led to promoter activation of the gene for an astrocyte marker, glial fibrillary acidic protein (GFAP), which was clearly inhibited by expressio n of a dominant negative form of a gp130-downstream transcription factor, s ignal transducer and activator of transcription 3(STAT3), or by introductio n of a mutation in a single STAT3-binding site in the promoter, suggesting a critical role of STAT3 in the CT-1-induced GFAP transcription. These resu lts suggest that astrocyte differentiation in the developing brain involves CT-1-signaling which cooperates with BMP2. (C) 2001 Academic Press.