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Development, Vol 127, Issue 3 543-548, Copyright © 2000 by Company of Biologists
JOURNAL ARTICLES |
SJ Karp, E Schipani, B St-Jacques, J Hunzelman, H Kronenberg and AP McMahon
Harvard University, Department of Molecular Biology, The Biolabs, Cambridge, MA 02138, USA.
Indian hedgehog (Ihh) and Parathyroid Hormone-related Protein (PTHrP) play a critical role in the morphogenesis of the vertebrate skeleton. Targeted deletion of Ihh results in short-limbed dwarfism, with decreased chondrocyte proliferation and extensive hypertrophy, features shared by mutants in PTHrP and its receptor. Activation of Ihh signaling upregulates PTHrP at the articular surface and prevents chondrocyte hypertrophy in wild-type but not PTHrP null explants, suggesting that Ihh acts through PTHrP. To investigate the relationship between these factors during development of the appendicular skeleton, mice were produced with various combinations of an Ihh null mutation (Ihh(-/-)), a PTHrP null mutation (PTHrP(-/-)), and a constitutively active PTHrP/Parathyroid hormone Receptor expressed under the control of the Collagen II promoter (PTHrPR*). PTHrPR* rescues PTHrP(-/-) embryos, demonstrating this construct can completely compensate for PTHrP signalling. At 18.5 dpc, limb skeletons of Ihh, PTHrP compound mutants were identical to Ihh single mutants suggesting Ihh is necessary for PTHrP function. Expression of PTHrPR* in chondrocytes of Ihh(-/-) mice prevented premature chondrocyte hypertrophy but did not rescue either the short-limbed dwarfism or decreased chondrocyte proliferation. These experiments demonstrate that the molecular mechanism that prevents chondrocyte hypertrophy is distinct from that which drives proliferation. Ihh positively regulates PTHrP, which is sufficient to prevent chondrocyte hypertrophy and maintain a normal domain of cells competent to undergo proliferation. In contrast, Ihh is necessary for normal chondrocyte proliferation in a pathway that can not be rescued by PTHrP signaling. This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh's actions.
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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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|
|
|
|
 |
|
 N Giordano, L Gennari, M Bruttini, F Mari, I Meloni, C Baldi, S Capoccia, S Geraci, D Merlotti, A Amendola, et al. Mild brachydactyly type A1 maps to chromosome 2q35-q36 and is caused by a novel IHH mutation in a three generation family J. Med. Genet., February 1, 2003; 40(2): 132 - 135. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
 |
|
 F. Chevy, F. Illien, C. Wolf, and C. Roux Limb malformations of rat fetuses exposed to a distal inhibitor of cholesterol biosynthesis J. Lipid Res., August 1, 2002; 43(8): 1192 - 1200. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
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|
|
|
|
|
|
R. A. Deckelbaum, G. Chan, D. Miao, D. Goltzman, and A. C. Karaplis Ihh enhances differentiation of CFK-2 chondrocytic cells and antagonizes PTHrP-mediated activation of PKA J. Cell Sci., July 15, 2002; 115(14): 3015 - 3025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Ornitz and P. J. Marie FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease Genes & Dev., June 15, 2002; 16(12): 1446 - 1465. [Full Text] [PDF]
|
|
|
|
|
|
Z. Liu, J. Xu, J. S. Colvin, and D. M. Ornitz Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18 Genes & Dev., April 1, 2002; 16(7): 859 - 869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Long, X. M. Zhang, S. Karp, Y. Yang, and A. P. McMahon Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation Development, December 15, 2001; 128(24): 5099 - 5108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Minina, H. M. Wenzel, C. Kreschel, S. Karp, W. Gaffield, A. P. McMahon, and A. Vortkamp BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation Development, November 15, 2001; 128(22): 4523 - 4534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
M. Sahni, R. Raz, J. D. Coffin, D. Levy, and C. Basilico STAT1 mediates the increased apoptosis and reduced chondrocyte proliferation in mice overexpressing FGF2 Development, June 1, 2001; 128(11): 2119 - 2129. [Abstract] [Full Text] [PDF]
|
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|
|
 |
|
 L. Chen, C. Li, W. Qiao, X. Xu, and C. Deng A Ser365{->}Cys mutation of fibroblast growth factor receptor 3 in mouse downregulates Ihh/PTHrP signals and causes severe achondroplasia Hum. Mol. Genet., March 1, 2001; 10(5): 457 - 465. [Abstract] [Full Text] [PDF]
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V. Krishnan, Y. L. Ma, J. M. Moseley, A. G. Geiser, S. Friant, and C. A. Frolik Bone Anabolic Effects of Sonic/Indian Hedgehog Are Mediated By BMP-2/4-Dependent Pathways in the Neonatal Rat Metatarsal Model Endocrinology, February 1, 2001; 142(2): 940 - 947. [Abstract] [Full Text] [PDF]
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M. Dyer, S. Farrington, D Mohn, J. Munday, and M. Baron Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo Development, January 5, 2001; 128(10): 1717 - 1730. [Abstract] [PDF]
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F Long, E Schipani, H Asahara, H Kronenberg, and M Montminy The CREB family of activators is required for endochondral bone development Development, January 2, 2001; 128(4): 541 - 550. [Abstract] [PDF]
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M Hebrok, S. Kim, B St Jacques, A. McMahon, and D. Melton Regulation of pancreas development by hedgehog signaling Development, January 11, 2000; 127(22): 4905 - 4913. [Abstract] [PDF]
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C Hartmann and C. Tabin Dual roles of Wnt signaling during chondrogenesis in the chicken limb Development, January 7, 2000; 127(14): 3141 - 3159. [Abstract] [PDF]
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T. Aikawa, G. V. Segre, and K. Lee Fibroblast Growth Factor Inhibits Chondrocytic Growth through Induction of p21 and Subsequent Inactivation of Cyclin E-Cdk2 J. Biol. Chem., July 27, 2001; 276(31): 29347 - 29352. [Abstract] [Full Text] [PDF]
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