ANALYSIS OF THE ROLES OF PBX1 AND EMX2 IN THE DEVELOPMENT OF THE SCAPULAR AND PELVIC REGIONS OF THE LIMBS

The genes and the genetic pathways controlling the development of the most proximal limb elements, the limb girdles, are still largely unknown. Also basically unknown are possible candidate genes responsible for human hereditary malformations of the proximal limb skeleton. Two human conditions are characterised by hereditary congenital malformations of the limb girdle skeletal elements, pelvis-shoulder dysplasia and pelviscapular dysplasia. In both conditions affected patients show marked reduction and malformation of specific limb girdle skeletal elements. Mouse animal models for two genes expressed in the most proximal regions of the limbs, Emx2 and Pbx1, have provided new insight into the possible genetic pathways controlling limb girdle formation. Impairment of Emx2 or Pbx1 function is associated with severe developmental defects of the limb girdles. Our study is aimed at the understanding of the possible interactions between these two crucial genes. We will use the available mouse models to study in living animals during embryonic development the interactions between these two genes. The completion of these studies will hopefully advance our understanding of the regulation of limb girdle formatio. Under a broader perspective this work will also hopefully impact on our understanding of the pathogenesis of human birth defects affecting the development of proximal limb skeletal elements.