Non‐molecular, epigenetic, physical factors in limb initiation

Abstract

A large body of evidence suggests that genes influence vertebrate limb position. However, many, if not all, of those genes concomitantly affect the position of the kidneys, umbilical artery, and end of the celom. Is limb position determined independently of those other structures or is its position dependent upon and determined by one or more of those other structures? It has been proposed that limbs form at the cranial and caudal ends of the yolk sac as the result of biomechanical forces. If such is the case, it may be that the genes affecting limb position may directly affect the length of the yolk sac, as reflected in a change in celom length, and that the change in yolk sac length, in a truly epigenetic, biomechanical fashion, determines limb position. If such is the case, we propose that by decreasing the length of the yolk sac–body axis interface we should be able to decrease the distance between the limbs. To test this hypothesis, we separated the caudal half of the yolk sac from the embryo axis in salamander embryos (Ambystoma tigrinum). Salamanders resulted with hindlimbs at the new caudal end of the trunk, four vertebrae cranial to the normal limb position. Our data suggest that limb placement is determined, at least in part, by biophysical constraints. J. Exp. Zool. 284:55–66, 1999. © 1999 Wiley-Liss, Inc.