03-P116 Identification of Hox genes that determine limb position

Tetrapods have two pairs of appendages, forelimbs and hindlimbs, that develop from fixed positions along the body axis; the forelimbs from the region of the cervical/thoracic junction and hindlimbs from the lumbar/sacral junction. While the number of vertebrae in each cervical/thoracic/lumbar/sacral territory can vary greatly among different species of vertebrates, the relative position of the limbs along the body axis is, however, conserved. There are two possible mechanisms that determine limb position. The rostral-caudal position of limb progenitors in the lateral plate mesoderm is instructed either autonomously or by the adjacent axial tissues. In some Hox mutant mice, the relative position of certain vertebrae and the limbs remains coordinated (van den Akker et al., 2001; McIntyre et al., 2007). These observations support the latter model. In some cases, however, limb position can be uncoupled from axial identity (Wellik et al., 2003). Therefore, the question remains whether identity of axial tissues influences limb positioning or if they are simply correlated. To examine this, we are using MLL (Trithorax-related) null mice in which the expression of several Hox genes is altered, and transgenic methods to misexpress candidate Hox genes in the lateral plate mesoderm.