Bone Biology & Therapeutics. Abstracts of the 2010 IBMS Davos Workshop. March 14-19, 2010. Davos, Switzerland.

摘要

The developing limb is an attractive model to study the mechanisms of skeletal patterning and growth. During early development the pattern of the future limb elements is determined by a three-dimensional coordinate system of signaling molecules including the families of Hox, Shh, FGF, and Wnt genes. Thereafter, chondrogenesis takes place, initiated by mesenchymal progenitor cells that adhere to each other and condense to form a template of the future bone. Hox genes have long been regarded as master regulators of early patterning processes, as demonstrated by the homeotic transformation phenotypes in Drosophila such as antennapedia and bithorax. In mammals they play important roles in the development of the limb and the spine and mutations in several HOX genes are associated with human limb malformations. For example, poly-alanine expansions in H0XD13 result in digit duplications and fusions (synpolydactyly, SPD). We used the mouse mutant synpolydactly homologe (spdh) to investigate the molecular pathogenesis of SPD. Spdh/spdh mice show multiple extra digits with fusions. Chondrocytes within the anlagen do not differentiate and bne formation does not take place until P7.