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Question

Which molecule establishes the dorsal-ventral axis of the limb?

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Explanation

Dorsal-ventral polarity originates from ectoderm-mesenchyme signaling interactions conserved across vertebrates and mammals. Dorsal ectoderm secretes Wnt7a, which via canonical beta-catenin pathway induces LIM-homeodomain factor Lmx1b in underlying dorsal mesenchyme, conferring dorsal character to skin, nails, sesamoids and extensor musculature. Ventral ectoderm expresses Engrailed-1, which represses Wnt7a, confining it dorsally and permitting ventral BMP-driven fate with thick volar pads. Loss of Wnt7a ventralizes dorsal limb causing biventral double-ventral phenotype. TBX5 specifies forelimb, Lmx1b executes dorsal program downstream, RA patterns proximal-distal axis.

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