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Development ePress online publication date 2 Dec 2004
doi: 10.1242/dev.01564
Research article
Sequential roles of Hedgehog and Wnt signaling in osteoblast development
Hongliang Hu,
Matthew J. Hilton,
Xiaolin Tu,
Kai Yu,
David M. Ornitz,
and
Fanxin Long*
* Author for correspondence (e-mail: flong{at}wustl.edu)
Signals that govern development of the osteoblast lineage are not well understood. Indian hedgehog (Ihh), a member of the hedgehog (Hh) family of proteins, is essential for osteogenesis in the endochondral skeleton during embryogenesis. The canonical pathway of Wnt signaling has been implicated by studies of Lrp5, a co-receptor for Wnt proteins, in postnatal bone mass homeostasis. In the present study we demonstrate that
-catenin, a central player in the canonical Wnt pathway, is indispensable for osteoblast differentiation in the mouse embryo. Moreover, we present evidence that Wnt signaling functions downstream of Ihh in development of the osteoblast lineage. Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development.
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|
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|

|
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|
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283(29):
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|
 |
|

|
 |

|
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|
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|
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[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H K Datta, W F Ng, J A Walker, S P Tuck, and S S Varanasi
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|
 |
|

|
 |

|
 |
 
C. Fontaine, W. Cousin, M. Plaisant, C. Dani, and P. Peraldi
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|
 |
|

|
 |

|
 |
 
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March 21, 2008;
283(12):
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|
 |
|

|
 |

|
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|
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|

|
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90(Supplement_1):
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|

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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
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|
 |
|

|
 |

|
 |
 
K. K. Mak, M.-H. Chen, T. F. Day, P.-T. Chuang, and Y. Yang
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September 15, 2006;
133(18):
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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August 15, 2006;
133(16):
3231 - 3244.
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[Full Text]
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|
 |
|

|
 |

|
 |
 
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August 1, 2006;
133(15):
3039 - 3049.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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[Abstract]
[Full Text]
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|
 |
|

|
 |

|
 |
 
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J. Biol. Chem.,
January 20, 2006;
281(3):
1381 - 1388.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Schipani, A. Zallone, G. J. Strewler, J. W. Pike, S. Ferrari, Y. Jiang, and E. Seeman
Meeting Report from the 27th Annual Meeting of the American Society for Bone and Mineral Research: September 23-27, 2005 in Nashville, Tennessee, USA
IBMS BoneKEy,
January 1, 2006;
3(1):
29 - 62.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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Development,
October 1, 2005;
132(19):
4339 - 4351.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Gaur, C. J. Lengner, H. Hovhannisyan, R. A. Bhat, P. V. N. Bodine, B. S. Komm, A. Javed, A. J. van Wijnen, J. L. Stein, G. S. Stein, et al.
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J. Biol. Chem.,
September 30, 2005;
280(39):
33132 - 33140.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
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M. Ai, S. L. Holmen, W. Van Hul, B. O. Williams, and M. L. Warman
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Mol. Cell. Biol.,
June 15, 2005;
25(12):
4946 - 4955.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
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T. Kobayashi and H. Kronenberg
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Endocrinology,
March 1, 2005;
146(3):
1012 - 1017.
[Abstract]
[Full Text]
[PDF]
|
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|

|
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|
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E. Seeman and G. J. Strewler
Clinical and Basic Research Papers - December 2004 Selections
IBMS BoneKEy,
January 1, 2005;
2(1):
1 - 5.
[Full Text]
[PDF]
|
 |
|
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