[Show abstract][Hide abstract] ABSTRACT: We have previously shown differential regulation of components of the Retinoic acid (RA) pathway in Xenopus tadpole hindlimb regeneration. RA is thought to act as a morphogen, providing positional information during development and regeneration. We have investigated the regulation of genes involved in RA synthesis, catabolism, and binding in developing and regenerating Xenopus limbs. Our data indicate that RA is synthesised by Raldh2 in proximal cells during limb bud outgrowth. Furthermore, Cyp26b is expressed transiently in the progress zone of developing limbs and the blastema of regenerating limbs suggesting degradation of RA occurs in both processes. The RA-binding protein Crabp2 is also upregulated during regeneration. We summarise this data to predict the presence of evolving gradients of RA in the developing amphibian limb. Thus, RA from the stump cells could be responsible for the establishment of proximal-distal pattern during limb regeneration, as predicted by classical studies.
[Show abstract][Hide abstract] ABSTRACT: Retinoic acid (RA) is a known teratogen that is also required endogenously for normal development of the embryo. RA can act as a morphogen, through direct binding to receptors and RA response elements in the genome, and classical studies of limb development and regeneration in amphibians have shown that it is likely to provide positional information. Availability of RA depends on both metabolic synthesis and catabolic degradation, and specific binding proteins act to further modulate the binding of RA to response elements. Here, we describe the expression of seven genes involved in metabolism (Raldh1-3), catabolism (Cyp26a and b) and binding of RA (Crabp1 and 2) during organogenesis in the clawed frog Xenopus laevis. Taken together, this data indicates regions of the embryo that could be affected by RA mediated patterning, and identifies some differences with other vertebrates.