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TISSUE-SPECIFIC STEM CELLS

Concise Review: Bone Morphogenetic Protein Pleiotropism in Neural Stem Cells and Their Derivatives—Alternative Pathways, Convergent Signals

Center for Neuroscience Research, Children's National Medical Center, Washington, DC, USA

Key Words. Apoptosis • TGF-ß receptor • Proliferation • Pleiotropic effects • Neural stem cell • Neural differentiation • Growth factor Bone morphogenetic protein • Bone morphogenetic protein receptor • Smad proteins • Mammalian target of rapamycin p38 mitogen-activated protein kinase • Neural crest

Correspondence: David M. Panchision, Ph.D., Children's National Medical Center, Center for Neuroscience Research, 111 Michigan Avenue NW, 5th Floor, Suite 5340, Washington, DC 20010, USA. Telephone: 202-884-2269; Fax: 202-884-4988; e-mail: dpanchision{at}cnmcresearch.org

Received June 2, 2006; accepted for publication September 7, 2006.
First published online in STEM CELLS EXPRESS   September 14, 2006.



Bone morphogenetic proteins (BMPs) are a class of morphogens that are critical regulators of the central nervous system (CNS), peripheral nervous system, and craniofacial development. Modulation of BMP signaling also appears to be an important component of the postnatal stem cell niche. However, describing a comprehensive model of BMP actions is complicated by their paradoxical effects in precursor cells, which include dorsal specification, promoting proliferation or mitotic arrest, cell survival or death, and neuronal or glial fate. In addition, in postmitotic neurons BMPs can promote dendritic growth, act as axonal chemorepellants, and stabilize synapses. Although many of these responses depend on interactions with other incoming signals, some reflect the recruitment of distinct BMP signal transduction pathways. In this review, we classify the diverse effects of BMPs on neural cells, focus on the known mechanisms that specify distinct responses, and discuss the remaining challenges in identifying the cellular basis of BMP pleiotropism. Addressing these issues may have importance for stem cell mobilization, differentiation, and cell integration/survival in reparative therapies.