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Normal patterning of the developing limb requires a tight restriction of Sonic hedgehog (Shh) mRNA to the posterior margin of the limb bud. While several positive and negative regulatory factors have been identified which serve to position the Shh expression domain in the distal posterior limb, these factors cannot in themselves explain the tight restriction of Shh to the posterior margin, nor can...
Proper outgrowth of the limb bud requires a positive feedback loop between Sonic hedgehog (Shh) in the zone of polarizing activity (ZPA) and Fgfs in the overlying apical ectodermal ridge. The Bmp antagonist Gremlin is expressed in a domain anterior to the ZPA and is thought to act as a signaling intermediate between Shh and Fgf. It is currently unclear whether Shh acts directly or indirectly to initiate...
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