TY - JOUR A1 - Hughes, Simon M. A1 - Lillien, Laura E. A1 - Raff, Martin C. A1 - Rohrer, Hermann A1 - Sendtner, Michael T1 - Ciliary neurotrophic factor induces type-2 astrocyte differentiation in culture N2 - We have been studying a population of bipotential glial progenitor cells in the perinatal rat optic nerve and brain in an attempt to understand how cells choose between alternative fates in the developing mammalian central nervous system (CNS). This cell population gives rise initially to oligodendrocytes and then to type-2 astrocytes1 both of which apparently collaborate in sheathing axons in the CNS2,3. In vitro studies suggest that oligodendrocyte differentiation is the constitutive pathway of development for the oligodendrocyte-type-2-astrocyte (O-2A) progenitor cell4,5, whereas type-2 astrocyte differentiation depends on a specific inducing protein6. This protein is present in the developing optic nerve when type-2 astrocytes are differentiating and can induce 0-2A progenitor cells in vitro to express glial fibrillary acidic protein (GFAP)6, a marker of astrocyte differentiation7. Here we show that the type-2-astrocyte-inducing protein is similar or identical to ciliary neutrotrophic factor (CNTF)8,9, which promotes the survival of some types of peripheral neurons in vitro8, including ciliary ganglion neurons8,10. This suggests that CNTF, in addition to its effect on neurons, may be responsible for triggering type-2 astrocyte differentiation in the developing CNS. Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42660 ER - TY - JOUR A1 - Lillien, Laura E. A1 - Sendtner, Michael A1 - Raff, Martin C. T1 - Extracellular Matrix-associated molecules collaborate with ciliary neurotrophic factor to induce type-2 astrocyte development N2 - 0-2A progenitor cells give rise to both oligodendrocytes and type-2 astrocytes in vitro. Whereas oligodendrocyte differentiation occurs constitutively, type-2 astrocyte differentiation requires extracellular signals, one of which is thought to be ciliary neurotrophic factor (CNTF). CNTF, however, is insufficient by itself to induce the development of stable type-2 astrocytes. In this report we show the following: (a) that molecules associated with the extracellular matrix (ECM) cooperate with CNTF to induce stable type-2 astrocyte differentiation in serumfree cultures. The combination of CNTF and the ECM-associated molecules thus mimics the effect of FCS, which has been shown previously to induce stable type-2 astrocyte differentiation in vitro. (b) Both the ECM-associated molecules and CNTF act directly on 0-2A progenitor cells and can induce them to differentiate prematurely into type-2 astrocytes. (c) ECM-associated molecules also inhibit oligodendrocyte differentiation, even in the absence of CNTF, but this inhibition is not sufficient on its own to induce type-2 astrocyte differentiation. (d) Whereas the effect of ECM on oligodendrocyte differentiation is mimicked by basic fibroblast growth factor (bFGF), the effect of ECM on type-2 astrocyte differentiation is not. (e) The ECM-associated molecules that are responsible for inhibitin~ oligodendrocyte differentiation and for cooperating with CNTF to induce type-2 astrocyte differentiation are made by non-glial cells in vitro. (f) Molecules that have these activities and bind to ECM are present in the optic nerve at the time type-2 astrocytes are thought to be developing. Y1 - 1990 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42602 ER - TY - JOUR A1 - Lillien, Laura E. A1 - Sendtner, Michael A1 - Rohrer, Hermann A1 - Hughes, Simon M. A1 - Raff, Martin C. T1 - Type-2 Astrocyte Development in Rat Brain Cultures is initiated by a CNTF-like protein produced by type-1 astrocytes N2 - No abstract available Y1 - 1988 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31708 ER -