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
Chen1, 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
Copyright © 2002 Society for Neuroscience 0270-6474/02/222310377-11$05.00/0