Pattern formation is the process that controls the spatial ordering of organs and differentiated cell types during development. Features of the mechanism of pattern formation are revealed when developing systems undergo pattern regulation. Developing and regenerating limbs show extensive regulative abilities and thus have long been used as models for pattern formation in vertebrates. The proposed experiments on regenerating axolotl limbs use a combination of in vivo and invitor approaches to investigate the ability of cells form one limb position to induce patterning and growth responses in cells at a different position. The induction of supernumerary pattern and growth will be used to investigate whether limb cells retain their positional properties in vitro, and whether the molecules associated with these properties can be detected in membranes, extracellular matrix or culture medium conditioned by cells from particular limb positions. We will examine the ability of retinoic acid to change anterior limb cells that function as posterior cells using both in vivo and in vitro approaches. Finally, the effects of TGF beta and a and b FGF, which have known effects on limb development, will be investigated for their role in pattern formation and position-dependent growth. It is anticipated that an understanding of pattern formation will allow for the development of strategies to stimulate controlled growth and pattern (regeneration); to inhibit unpatterned, uncontrolled growth (cancer) and to correct abnormal pattern (birth defects).
