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Publication : Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway.

First Author  Fernandez-Teran M Year  2000
Journal  Development Volume  127
Issue  10 Pages  2133-42
PubMed ID  10769237 Mgi Jnum  J:61522
Mgi Id  MGI:1355128 Doi  10.1242/dev.127.10.2133
Citation  Fernandez-Teran M, et al. (2000) Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the sonic hedgehog pathway. Development 127(10):2133-42
abstractText  dHAND is a basic helix-loop-helix (bHLH) transcription factor essential for cardiovascular development. Here we analyze its pattern of expression and functional role during chick limb development. dHAND expression was observed in the lateral plate mesoderm prior to emergence of the limb buds. Coincident with limb initiation, expression of dHAND became restricted to the posterior half of the limb bud. Experimental procedures that caused mirror-image duplications of the limb resulted in mirror-image duplications of the pattern of dHAND expression along the anterior-posterior axis. Retroviral overexpression of dHAND in the limb bud produced preaxial polydactyly, corresponding to mild polarizing activity at the anterior border. At the molecular level, misexpression of dHAND caused ectopic activation of members of the Sonic hedgehog (Shh) pathway, including Gli and Patched, in the anterior limb bud. A subset of infected embryos displayed ectopic anterior activation of Shh. Other factors implicated in anterior-posterior polarization of the bud such as the most 5' Hoxd genes and Bmp2 were also ectopically activated at the anterior border. Our results indicate a role for dHAND in the establishment of anterior-posterior polarization of the limb bud.
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