The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the limbs of these mice have several similarities with En1 mutant mice which have a double-dorsal phenotype. however, we show that appropriate dorsoventral limb pattern is maintained at the molecular level and that the observed defects are due to a failure to appropriately execute ventral pattern. Additionally, newborn mice lack ventral digital tendons and the most superficial musculature in the regions of strongest and earliest deletion. Molecular analysis indicates that tendons are lost downstream of the absent musculature and are initially patterned correctly. Thus we show a role for ectodermal Wnts in the development of underlying musculature. We additionally examine the role of limb mesenchymal Wnts in the development of deeper limb musculature utilizing the Prx1Cre deleter. The deep musculature of the autopod and zeugopod is reduced or absent in mutants and the development of superficial musculature appears to proceed normally. Hence we show that superficial muscles require only ectodermal Wnts and deeper muscles require only mesenchymal Wnts.



College and Department

Life Sciences; Physiology and Developmental Biology



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porcupine, wnt, muscle, development, limbs, anus, abdomen, tcf4