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The Journal of Neuroscience, December 1, 2002, 22(23):10377-10387

Glia Induce Dendritic Growth in Cultured Sympathetic Neurons by Modulating the Balance between Bone Morphogenetic Proteins (BMPs) and BMP Antagonists

Pamela J. Lein¹, Hiroko Nagasawa Beck¹, Vidya Chandrasekaran², Patrick J. Gallagher³, Hui-Ling Chen^{1, 4}, Yuan Lin⁵, Xin Guo¹, Paul L. Kaplan⁶, Henri Tiedge⁵, and Dennis Higgins²

¹ Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, ² Department of Pharmacology and Toxicology, State University of New York, Buffalo, New York 14214, ³ Department of Biology, Canisius College, Buffalo, New York 14208, ⁴ Graduate Institute of Life Sciences, National Defense Medical Center, National Defense University, Taipei, Taiwan, ⁵ Department of Physiology and Pharmacology, State University of New York, Brooklyn, New York 11203, and ⁶ Creative Biomolecules, Inc., Hopkinton, Massachusetts 01748

Dendritic growth in cultured sympathetic neurons requires specific trophic interactions. Previous studies have demonstrated that either coculture with glia or exposure to recombinant bone morphogenetic proteins (BMPs) is both necessary and sufficient to induce dendrite formation. These observations led us to test the hypothesis that BMPs mediate glial-induced dendritic growth. In situ hybridization and immunocytochemical studies indicate that the spatiotemporal expression of BMP5, -6, and -7 in rat superior cervical ganglia (SCG) is consistent with their proposed role in dendritogenesis. In vitro, both SCG glia and neurons were found to express BMP mRNA and protein when grown in the presence or absence of the other cell type. However, addition of ganglionic glia to cultured sympathetic neurons causes a marked increase in BMP proteins coincident with a significant decrease in follistatin and noggin. Functional assays indicate that glial-induced dendritic growth is significantly reduced by BMP7 antibodies and completely inhibited by exogenous noggin and follistatin. These data suggest that glia influence the rapid perinatal expansion of the dendritic arbor in sympathetic neurons by increasing BMP activity via modulation of the balance between BMPs and their antagonists.

Key words: BMPs; BMP antagonists; noggin; follistatin; dendrites; sympathetic neurons; neuron-glia interactions

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Copyright © 2002 Society for Neuroscience  0270-6474/02/222310377-11$05.00/0

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