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The Journal of Neuroscience, March 15, 1999, 19(6):2113-2121

Leukemia Inhibitory Factor and Ciliary Neurotrophic Factor Cause Dendritic Retraction in Cultured Rat Sympathetic Neurons

Xin Guo¹, Vidya Chandrasekaran¹, Pamela Lein², Paul L. Kaplan³, and Dennis Higgins¹

¹ Department of Pharmacology and Toxicology, State University of New York, Buffalo, New York 14214, ² Department of Biology, Canisius College, Buffalo, New York 14208, and ³ Creative Biomolecules, Inc., Hopkinton, Massachusetts 01748

Dendritic retraction occurs in many regions of the developing brain and also 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 sympathetic neurons to retract their dendrites in vitro, ultimately leading to an ~80% reduction in the size of the arbor. The dendritic retraction induced by LIF exhibited substantial specificity because it was not accompanied by changes in cell number, in the rate of axonal growth, or in the expression of axonal cytoskeletal elements. An antibody to gp130 blocked the effects of LIF and CNTF, and both cytokines induced phosphorylation and nuclear translocation of stat3. Moreover, addition of soluble interleukin-6 (IL-6) receptor to the medium endowed IL-6 with the ability to cause dendritic regression. These data indicate that ligands activating the gp130 pathway have the ability to profoundly alter neuronal cell shape and polarity by selectively causing the retraction of dendrites.

Key words: leukemia inhibitory factor; ciliary neurotrophic factor; osteogenic protein-1; bone morphogenetic protein; dendritic retraction; dendrites; sympathetic neurons; stat3; gp130

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Copyright © 1999 Society for Neuroscience  0270-6474/99/1962113-09$05.00/0

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