Diplopodia - Causes

Causes

Recessive alleles of some genes involved in embryonic limb patterning produce bilateral diplopodia, and diplopodia can be experimentally induced in early embryos. Many instances of diplopodia in humans have no apparent cause.

People have been able to produce diplopod limbs by increasing sonic hedgehog (shh) signaling in the limb buds of embryos. The zone of polarizing activity (ZPA) in the proximal posterior mesoderm of a tetrapod limb bud is responsible for maintaining the anterior-posterior axis of the growing limb. The ZPA secretes shh protein, which induces formation of the distal segment of the limb, or autopod, with its posterior side facing the ZPA. When ZPA cells, non-ZPA cells made to express shh, or simply shh protein-soaked beads are implanted in the anterior side of a limb bud, the end of the resulting limb is duplicated, as in diplopodia. The posterior autopod on that limb has the normal orientation, and the extra, anterior autopod has a reversed anterior-posterior axis. This is because the original ZPA and the added source of shh signaling each induce the formation of an autopod.

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