Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 14 July 2000:
Vol. 289. no. 5477, pp. 313 - 316
DOI: 10.1126/science.289.5477.313

Reports

Induction and Maintenance of the Neuronal Cholinergic Phenotype in the Central Nervous System by BMP-9

Ignacio López-Coviella, 1 Brygida Berse, 2 Raul Krauss, 3 R. Scott Thies, 3 Jan Krzysztof Blusztajn 12*

Bone morphogenetic proteins (BMPs) have multiple functions in the developing nervous system. A member of this family, BMP-9, was found to be highly expressed in the embryonic mouse septum and spinal cord, indicating a possible role in regulating the cholinergic phenotype. In cultured neurons, BMP-9 directly induced the expression of the cholinergic gene locus encoding choline acetyltransferase and the vesicular acetylcholine transporter and up-regulated acetylcholine synthesis. The effect was reversed upon withdrawal of BMP-9. Intracerebroventricular injection of BMP-9 increased acetylcholine levels in vivo. Although certain other BMPs also up-regulated the cholinergic phenotype in vitro, they were less effective than BMP-9. These data indicate that BMP-9 is a differentiating factor for cholinergic central nervous system neurons.

1 Department of Psychiatry and
2 Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
3 Genetics Institute, Cambridge, MA 02140, USA.
*   To whom correspondence should be addressed. E-mail: jbluszta{at}bu.edu


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
SUMO Interaction Motifs in Sizn1 Are Required for Promyelocytic Leukemia Protein Nuclear Body Localization and for Transcriptional Activation.
G. Cho, Y. Lim, and J. A. Golden (2009)
J. Biol. Chem. 284, 19592-19600
   Abstract »    Full Text »    PDF »
Hey1 Basic Helix-Loop-Helix Protein Plays an Important Role in Mediating BMP9-induced Osteogenic Differentiation of Mesenchymal Progenitor Cells.
K. A. Sharff, W.-X. Song, X. Luo, N. Tang, J. Luo, J. Chen, Y. Bi, B.-C. He, J. Huang, X. Li, et al. (2009)
J. Biol. Chem. 284, 649-659
   Abstract »    Full Text »    PDF »
Modulation of Bone Morphogenetic Protein-9 Expression and Processing by Insulin, Glucose, and Glucocorticoids: Possible Candidate for Hepatic Insulin-Sensitizing Substance.
L. C. Caperuto, G. F. Anhe, T. D. Cambiaghi, E. H. Akamine, D. do Carmo Buonfiglio, J. Cipolla-Neto, R. Curi, and S. Bordin (2008)
Endocrinology 149, 6326-6335
   Abstract »    Full Text »    PDF »
Bone Morphogenetic Protein-9 Induces Apoptosis in Prostate Cancer Cells, the Role of Prostate Apoptosis Response-4.
L. Ye, H. Kynaston, and W. G. Jiang (2008)
Mol. Cancer Res. 6, 1594-1606
   Abstract »    Full Text »    PDF »
Regulation of Cholinergic Phenotype in Developing Neurons.
X. Liu, I. R. Popescu, J. V. Denisova, R. L. Neve, R. A. Corriveau, and A. B. Belousov (2008)
J Neurophysiol 99, 2443-2455
   Abstract »    Full Text »    PDF »
Sizn1 Is a Novel Protein That Functions as a Transcriptional Coactivator of Bone Morphogenic Protein Signaling.
G. Cho, Y. Lim, D. Zand, and J. A. Golden (2008)
Mol. Cell. Biol. 28, 1565-1572
   Abstract »    Full Text »    PDF »
BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis.
M. Scharpfenecker, M. van Dinther, Z. Liu, R.L. van Bezooijen, Q. Zhao, L. Pukac, C. W. G. M. Lowik, and P. ten Dijke (2007)
J. Cell Sci. 120, 964-972
   Abstract »    Full Text »    PDF »
Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells.
L. David, C. Mallet, S. Mazerbourg, J.-J. Feige, and S. Bailly (2007)
Blood 109, 1953-1961
   Abstract »    Full Text »    PDF »
Crystal Structure of BMP-9 and Functional Interactions with Pro-region and Receptors.
M. A. Brown, Q. Zhao, K. A. Baker, C. Naik, C. Chen, L. Pukac, M. Singh, T. Tsareva, Y. Parice, A. Mahoney, et al. (2005)
J. Biol. Chem. 280, 25111-25118
   Abstract »    Full Text »    PDF »
Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons.
I. Lopez-Coviella, M. T. Follettie, T. J. Mellott, V. P. Kovacheva, B. E. Slack, V. Diesl, B. Berse, R. S. Thies, and J. K. Blusztajn (2005)
PNAS 102, 6984-6989
   Abstract »    Full Text »    PDF »
Inhibitor of DNA Binding/Differentiation Helix-Loop-Helix Proteins Mediate Bone Morphogenetic Protein-induced Osteoblast Differentiation of Mesenchymal Stem Cells.
Y. Peng, Q. Kang, Q. Luo, W. Jiang, W. Si, B. A. Liu, H. H. Luu, J. K. Park, X. Li, J. Luo, et al. (2004)
J. Biol. Chem. 279, 32941-32949
   Abstract »    Full Text »    PDF »
Autonomic microganglion cells: a source of acetylcholine in the rat carotid body.
E. B. Gauda, R. Cooper, S. M. Johnson, G. L. McLemore, and C. Marshall (2004)
J Appl Physiol 96, 384-391
   Abstract »    Full Text »    PDF »
Retrograde Gbb signaling through the Bmp type 2 receptor Wishful Thinking regulates systemic FMRFa expression in Drosophila.
G. Marques, T. E. Haerry, M. L. Crotty, M. Xue, B. Zhang, and M. B. O'Connor (2003)
Development 130, 5457-5470
   Abstract »    Full Text »    PDF »
Osteogenic Activity of the Fourteen Types of Human Bone Morphogenetic Proteins (BMPs).
H. Cheng, W. Jiang, F. M. Phillips, R. C. Haydon, Y. Peng, L. Zhou, H. H. Luu, N. An, B. Breyer, P. Vanichakarn, et al. (2003)
J. Bone Joint Surg. Am. 85, 1544-1552
   Abstract »    Full Text »    PDF »
The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain.
Y. Zhao, O. Marin, E. Hermesz, A. Powell, N. Flames, M. Palkovits, J. L. R. Rubenstein, and H. Westphal (2003)
PNAS 100, 9005-9010
   Abstract »    Full Text »    PDF »
Statins and the prevention of dementia.
U. N. Das (2001)
Can. Med. Assoc. J. 165, 908-909
   Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)