UC Irvine

The expression of Hox complex genes in correct spatial and temporal order is critical to patterning of the body axis and limbs during embryonic development. In order to understand the role such genes play in appendage regeneration, we have compared the expression of two 5' Hox complex genes: Hoxb13 and Hoxc10 during development and regeneration of the body axis and the limbs of axolotls. In contrast to higher vertebrates, Hoxb13 is expressed not only in the tip of the developing tail, but also in the distal mesenchyme of developing hind limbs, and at low levels in developing forelimbs. Hoxc10 is expressed as two transcripts during both development and regeneration. The short transcript (Hoxc10S) is expressed in the tip of the developing tail, in developing hind limbs, and at low levels in developing forelimbs. The long transcript (Hoxc10L) is expressed in a similar pattern, with the exception that no expression in developing forelimbs could be detected. Hoxb13 and both transcripts of Hoxc10 are expressed at high levels in the regenerating spinal cord during tail regeneration, and in both regenerating hind limbs and forelimbs. The up-regulation of expression of these genes during forelimb regeneration, relative to the very low levels of expression during forelimb development, suggests that they play a critical and perhaps unique role in regeneration. This is particularly true for Hoxc10L, which is not expressed during forelimb development, but is expressed during forelimb regeneration; thus making it the first truly "regeneration-specific" gene transcript identified to date.