EXPRESSION OF HOXD GENES IN DEVELOPING AND REGENERATING AXOLOTL LIMBS

Hox genes play a critical role in the development of the vertebrate ax is and limbs, and previous studies have implicated them in the specifi cation of positional identity, the control of growth, and the timing o f differentiation. Axolotl limbs offer an opportunity to distinguish t hese alternatives because the sequence of skeletal differentiation is reversed along the anterior-posterior axis relative to that of other t etrapods. We report that during early limb development, expression pat terns of HoxD genes in axolotls resemble those in amniotes and anuran amphibians. At later stages, the anterior boundary of Hoxd-11 expressi on is conserved with respect to morphological landmarks, but there is no anterior- distal expansion of the posterior domain of Hoxd-11 expre ssion similar to that observed in mice and chicks. Since axolotls do n ot form an expanded paddle-like handplate prior to digit differentiati on, we suggest that anterior expansion of expression in higher vertebr ates is linked to the formation of the handplate, but is clearly not n ecessary for digit differentiation. We also show that the 5' HoxD gene s are reexpressed during limb regeneration. The change in the expressi on pattern of Hoxd-11 during the course of regeneration is consistent with the hypothesis that the distal tip of the regenerate is specified first, followed by intercalation of intermediate levels of the patter n. Both Hoxd-8 and Hoxd-10 are expressed in non-regenerating wounds, b ut Hoxd-11 is specific for regeneration. It is also expressed in the p osterior half of nerve-induced supernumerary outgrowths. (C) 1998 Acad emic Press.