Leukemia inhibitory factor and ciliary neurotrophic factor cause dendriticretraction in cultured rat sympathetic neurons

Dendritic retraction occurs in many regions of the developing brain and als o after neural injury. However, the molecules that regulate this important regressive process remain largely unknown. Our data indicate that leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) cause sympat hetic neurons to retract their dendrites in vitro, ultimately leading to an similar to 80% reduction in the size of the arbor. The dendritic retractio n induced by LIF exhibited substantial specificity because it was not accom panied by changes in cell number, in the rate of axonal growth, or in the e xpression of axonal cytoskeletal elements. An antibody to gp130 blocked the effects of LIF and CNTF, and both cytokines induced phosphorylation and nu clear translocation of stat3. Moreover, addition of soluble interleukin-6 ( IL-6) receptor to the medium endowed IL-6 with the ability to cause dendrit ic regression. These data indicate that ligands activating the gp130 pathwa y have the ability to profoundly alter neuronal cell shape and polarity by selectively causing the retraction of dendrites.