ABSTRACT
We discuss the nature of positional information in the regenerating limb and that it is considered to be a cell surface-based system rather than one based on detection of extracellular gradients as thought to operate in development. The most informative approach to elaborating the genetic and molecular basis of positional information in limb regeneration has been experiments based on the application of precise concentrations of retinoic acid (RA) to regenerating blastemal cells. RA can respecify distal cells to become proximal cells. Since RA is an endogenous molecule that is required in the blastema and it acts through RA receptors in the nucleus, identifying the genes induced by RA during respecification will tell us about the molecular nature of positional information. Two experiments have so far attempted this and in one, a glycosylphosphatidylinisotol (GPI)-linked cell surface molecule called Prod 1 was identified, which acts through the Meis genes to alter the position of blastemal cells. In the other experiment, many genes were identified, including some known to be involved in proximal identity in the developing limb such as Meis genes and some that were repressed such as distal Hox genes. We draw these experiments together to reveal that we have a beginning of an understanding of the complexities of how regenerating limb blastemal cells might measure their position and suggest future directions in investigations of the remarkable cellular property of positional information.
