Leukemia inhibitory factor and ciliary neurotrophic factor regulate dendritic growth in cultures of rat sympathetic...

Cytokines such as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have previously been shown to regulate neurotransmitter and neuropeptide synthesis in sympathetic neurons [P.H. Patterson, Leukemia inhibitory factor, a cytokine at the interface between neurobiology and immunology, Proc. Natl. Acad. Sci. USA 91 (1994) 7833-7835]. We considered the possibility that these agents may also affect the development of neuronal cell shape. Intracellular dye injection and immunocytochemistry were used to assess dendritic growth in cultures of perinatal rat sympathetic neurons and the effects of LIF and CNTF were compared to those of osteogenic protein-1 (OP-1), a growth factor that induces profuse dendritic growth in these neurons [P. Lein, M. Johnson, X. Guo, D. Rueger, D. Higgins, Osteogenic protein-1 induces dendritic growth in rat sympathetic neurons, Neuron 15 (1995) 597-605]. Under control conditions, sympathetic neurons formed only axons. Exposure to either LIF or OP-1 stimulated dendritic growth, but the magnitude of the response to LIF was much less than that obtained with OP-1 with respect to both dendritic number and length. Simultaneous exposure to LIF and OP-1 resulted in dendritic growth equivalent to that observed in the presence of LIF alone, suggesting that LIF inhibits the response of neurons to OP-1. Both the stimulatory and inhibitory effects of LIF were mimicked by CNTF, but not by other growth factors. These data suggest that LIF and CNTF regulate dendritic development in a complex manner that is dependent on both the morphological state of the neuron and the presence of other growth factors. However, the net effect of exposure to these cytokines appears to be the production of a population of neurons with rudimentary arbors consisting of only one or two short dendrites.