Anterior to posterior patterning in the limb bud is determined by the zone of polarizing activity (ZPA). It resides at the posterior margin of the apical ectodermal ridge at the most distal point of the developing limb bud. The ZPA produces a protein which has a concentration gradient from posterior to anterior.
Transplantion of the ZPA to the opposite side of the limb bud produces a mirror limb - duplication along the radioulnar axis.
It is thought that the protein product of the gene sonic hedgehog is intimately involved in AP patterning. Application of exogenous gene product to the anterior limb limb bud results in duplication, mimicking the effect of the ZPA. Alternatively, the gene is upstream of a secondary, but yet unknown, soluble factor which also creates a concentration gradient.
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