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MBC in Press, published online ahead of print June 11, 2004
Mol. Biol. Cell 10.1091/mbc.E03-08-0584

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Submitted on August 12, 2003
Revised on May 31, 2004
Accepted on June 2, 2004

The Bone Morphogenetic Protein Type Ib Receptor is a Major Mediator of Glial Differentiation and Cell Survival in Adult Hippocampal Progenitor Cell Culture

A. Brederlau*{dagger}, R. Faigle*{ddagger}, M. Elmi*{ddagger}, A. Zarebski*{sect}, S. Sjöberg*, M. Fujii||, K. Miyazono||, and K. Funa*

*Institute of Anatomy and Cell Biology, Göteborg University, SE-405 30 Gothenburg, Sweden; {sect}Jagiellonian University, Faculty of Biotechnology, 30-387 Krakow, Poland; ||Department of Molecular Pathology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Monitoring Editor: Carl-Henrik Heldin

Bone morphogenetic proteins (BMPs) act as growth regulators and inducers of differentiation. They transduce their signal via three different type I receptors, termed activin receptor-like kinase 2 (Alk2), Alk3 or bone morphogenetic protein receptor Ia (BMPRIa) and Alk6 or BMPRIb. Little is known about functional differences between the three type I receptors. Here we have investigated consequences of constitutively active (ca) and dominant negative (dn) type I receptor overexpression in adult derived hippocampal progenitor cells (AHPs). The dn receptors have a nonfunctional intracellular, but functional extracellular domain. They thus trap BMPs that are endogenously produced by AHPs. We found that effects obtained by overexpression of dnAlk2 and dnAlk6 were similar, suggesting similar ligand binding patterns for these receptors. Thus, cell survival was decreased, glial fibrillary acidic protein (GFAP) expression was reduced while the number of oligodendrocytes increased. No effect on neuronal differentiation was seen. While the expression of Alk2 and Alk3 mRNA remained unchanged, the Alk6 mRNA was induced after impaired BMP signaling. After dnAlk3 overexpression, cell survival increased in parallel to augmented Alk6 receptor signaling. We conclude that endogenous BMPs mediate the survival of glial progenitors and suppress oligodendrocyte development mainly via the Alk6 receptor in AHP culture.

{ddagger}These authors contributed equally to this work. {dagger}Corresponding author. E-mail: anke.brederlau{at}anatcell.gu.se




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