Abstract
The various Wnt pathways that are related to upper limb anomalies are reviewed. Abnormalities in the Wnt7a pathway (located in the dorsal ectoderm) produce several clinically relevant conditions such as the palmar duplication syndrome, nail patella syndrome, ulnar ray deficiency, limb hypoplasia, polysyndactyly and the palmar nail syndrome. Abnormalities of the Wnt3/3a pathway (located in the apical ectodermal ridge) include tetra-amelia and loss of the distal phalanges/nails. Abnormalities of the Wnt5/5a pathway (located in the apical ectodermal ridge as well as in the mesoderm) will affect chondrogenesis of the developing limb and experimental Wnt5a(-/-) limbs have terminal adactyly. Chondrogenesis and limb muscle differentiation are both affected by several Wnt pathways and these will be reviewed in details. Abnormalities in LRP 5/6 (a co-receptor for Wnts) lead to congenital bone disease and Wnt4 is specifically involved in joint development. Finally, the relationship between the Wnt pathway and SALL4 (mutations of which cause Okihiro/Duane-radial ray deficiency in humans) are discussed.