Sonic hedgehog (shh) expression is detectable in the posterior mesenchyme o
f many developing vertebrate limbs. We have isolated an RT-PCR fragment fro
m the axolotl, Ambystoma mexicanum, that has high identity to other vertebr
ate shh genes. We describe the localization of this transcript during devel
opment and regeneration and in response to tissue grafts and retinoic acid
(RA) exposure in the axolotl. Even though axolotl digits show a reversed po
larity of differentiation (anterior [A] to posterior [P]) when compared to
other tetrapods (P to A), shh is nevertheless expressed on the posterior ma
rgin of developing and regenerating limb buds. When A cells are grafted adj
acent to P cells, an ectopic domain of shh is induced. Exposure to retinoic
acid (RA), a molecule known to alter pattern in all three limb axes in uro
deles, results in ectopic expression of shh in anterior cells of the regene
ration blastema. Prior to this induced expression in response to RA, there
is an earlier response by the endogenous domain of shh, which is downregula
ted within the first few hours of exposure. J. Exp. Zool. 284:197-206, 1999
. (C) 1999 Wiley-Liss, Inc.