Which signaling pathway primarily regulates the dorsal-ventral patterning of limbs?
Dorsal-ventral limb patterning determining dorsal nail, hair, and extensor versus ventral pad, sole, and flexor fates is regulated by Wnt7a secreted from dorsal ectoderm. Wnt7a induces LMX1B transcription factor in dorsal mesenchyme imposing dorsal characteristics, while ventral ectoderm expresses Engrailed-1 which represses Wnt7a ventrally permitting ventral identity. Sonic hedgehog governs anterior-posterior axis, BMP promotes ventral ectoderm and interdigital apoptosis, FGF10 initiates budding. Wnt7a knockout transforms dorsal into ventral, yielding double-ventral bi-ventral limbs with footpads dorsally and absent nails. Conserved across chick mouse human models, this mechanism illustrates classic embryological principles integrated with modern molecular genetics.
Ref: Gilbert, Developmental Biology, 12th ed., Chapter 19: Dorsoventral patterning – Wnt7a and Lmx1b dorsal specification.