Perspective: A suggested role for basement membrane structures during newt limb regeneration

Abstract

Background: Interactions between epithelium and mesenchyme, which occur across a basement membrane (BM) zone, are essential to generate a growth bud, or blastema, from which a new limb regenerates. An intact BM at that interface is believed to inhibit regeneration, but that mechanism of inhibition is not understood. Methods: Interference contrast microscopy and antibodies to laminin have been used to describe reformation of the BM and the basal lamina (BL) and their relationships to wound epithelium and mesenchyme in successive stages of blastema formation. Results: The BL is initially absent from the amputation surface and is reestablished to continuity by the late bud stage of regeneration. It forms generally from base to apex, precedes reticular lamina (RL) formation, and is absent beneath most of the wound epithelium. Our inability to correlate mesenchymal cell accumulation exclusively with the area lacking BL apically and postaxially prompted rethinking of the significance of the BL. Conclusions: Consistent with these and other observations, we suggest that the BL, when it forms during blastema formation, appears to function as in other developing systems to stabilize the phenotype of adjacent cells. Thus, epithelium becomes epidermis and adjacent mesenchyme synthesizes RL and becomes dermis. Accordingly, the feature that distinguishes regenerating from nonregenerating appendages is the ability of regenerating appendages to delay BL closure until after a critical mass of mesenchymal cells has accumulated.