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Development, Vol 121, Issue 12 4329-4337, Copyright © 1995 by Company of Biologists
JOURNAL ARTICLES |
A Hardy, MK Richardson, PH Francis-West, C Rodriguez, JC Izpisua-Belmonte, D Duprez and L Wolpert
Department of Anatomy and Developmental Biology, University College London, UK.
The developing chick limb has two major signalling centres; the apical ectodermal ridge maintains expression of several important genes and outgrowth of the limb, and the polarising region specifies the pattern of skeletal elements along the anteroposterior axis. We have used reaggregated leg grafts (mesenchyme dissociated into single cells, placed in an ectodermal jacket and grafted to a host) to study patterning in a system where the developmental axes are severely disrupted. Reaggregates from different regions of leg mesenchyme developed correspondingly different digits, giving a system in which skeletal phenotype could be compared with the expression of genes thought to be important in patterning. We found that posterior third and whole leg reaggregates gave rise to different digits, yet expressed the same combination of HoxD, Bmp-2 and shh genes throughout their development. Anterior thirds initially only express the 3' end of the HoxD cluster but activate the more 5' members of the cluster sequentially over a period of 48 hours, a period during which Bmp-2 is activated but no shh or Fgf-4 expression could be detected. Our results suggest that there are two independent mechanisms for activating the HoxD complex, one polarising region-dependent and one independent, and that shh expression may not be necessary to maintain outgrowth and patterning once a ridge has been established.
This article has been cited by other articles:
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  P. Francis-West and R. Hill Uncoupling the Role of Sonic Hedgehog in Limb Development: Growth and Specification Sci. Signal., July 1, 2008; 1(26): pe34 - pe34. [Abstract] [Full Text] [PDF]
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 K. Lewis, G Drossopoulou, I. Paton, D. Morrice, K. Robertson, D. Burt, P. Ingham, and C Tickle Expression of ptc and gli genes in talpid3 suggests bifurcation in Shh pathway Development, January 6, 1999; 126(11): 2397 - 2407. [Abstract] [PDF]
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M. Richardson, S. Allen, G. Wright, A Raynaud, and J Hanken Somite number and vertebrate evolution Development, January 1, 1998; 125(2): 151 - 160. [Abstract] [PDF]
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V Knezevic, R De Santo, K Schughart, U Huffstadt, C Chiang, K. Mahon, and S Mackem Hoxd-12 differentially affects preaxial and postaxial chondrogenic branches in the limb and regulates Sonic hedgehog in a positive feedback loop Development, January 11, 1997; 124(22): 4523 - 4536. [Abstract] [PDF]
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M. Ros, A Lopez-Martinez, B. Simandl, C Rodriguez, J. Izpisua Belmonte, R Dahn, and J. Fallon The limb field mesoderm determines initial limb bud anteroposterior asymmetry and budding independent of sonic hedgehog or apical ectodermal gene expressions Development, January 8, 1996; 122(8): 2319 - 2330. [Abstract] [PDF]
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D. Duprez, K Kostakopoulou, P. Francis-West, C Tickle, and P. Brickell Activation of Fgf-4 and HoxD gene expression by BMP-2 expressing cells in the developing chick limb Development, January 6, 1996; 122(6): 1821 - 1828. [Abstract] [PDF]
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