LEUKEMIA INHIBITORY FACTOR OR RELATED FACTORS PROMOTE THE DIFFERENTIATION OF NEURONAL AND ASTROCYTIC PRECURSORS WITHIN THE DEVELOPING MURINE SPINAL-CORD

Previously we have shown that leukaemia inhibitory factor (LIF) potent iates the development of murine spinal cord neurons in vitro, suggesti ng that it, or related factors, may play an important regulatory role in neuronal development. We have further investigated this role and sh ow here that the generation of neurons in cultures of embryonic day In spinal cord cells is inhibited by antibodies to the beta subunit of t he LIF receptor. Since there are more undifferentiated precursors in a ntibody-treated cultures than in control and LIF-treated cultures, it is concluded that the primary action of LIF, or related molecules, is to promote neuronal differentiation, not precursor survival, In additi on, the failure of LIF to support neuronal survival in the period imme diately following differentiation suggests that the increased numbers of neurons generated with LIF are not attributable to its neurotrophic action. By selecting neuronal precursors on the basis of their inabil ity to express class I major histocompatibility complex molecules, it was shown that LIF acted directly upon these cells and not via an inte rmediary cell. LIF also appears to be involved in regulating the diffe rentiation of astrocytes, since it increases the number of glial fibri llary protein (GFAP)-positive cells present in the cultures and since the spontaneous production of GFAP-positive cells is blocked by antibo dies to the LIF beta receptor. These findings suggest that LIF or rela ted factors promote the differentiation of neural precursors in the sp inal cord, but that they. are not involved in preferentially promoting precursors down a specific differentiation pathway.