Epidermal‐mesodermal interaction during morphogenesis of the limb regeneration blastema in larval salamanders

Abstract

The question was asked whether the proximo-distal regional organization of regenerating urodele limbs is the result of a n epidermal-mesodermal interaction, as is the case i n the embryonic limb bud, Epidermal deletion experiments on regeneration blastemas of various stages have answered this question i n the affirmative. The mechanisms involved in the morphogenesis of the regeneration blastema are therefore very similar to those operating in the morphogenesis of embryonic limb buds.

The interaction between the blastema and stump in the establishment of the anterior-posterior and proximal-distal organization of the limb regenerate

“…Complete re-DISCUSSION regeneration and overgrowth is very unThe results presented here show that, likely because the two limb levels used as despite the capacity of limb blastemas to transplantation sites were very similar in undergo selfdifferentiation (Stocum, 1968; cross-sectional area, leading in almost all de Both, 1970;Stocum and Dearlove, 1972; cases to a very good fit between transplant Faber, 19711, the stump and blastema do and stump. However, it is not unlikely that interact when they are adjacent to each some mixing of cells from the stump with other.…”

“…Although the mechanism by which the proximal-distal sequence of structures becomes specified within a growing blastema is unknown, Stocum and Dearlove (1972) have shown that young blastemas transplanted to a nonlimb ("indifferent") region of the body under conditions which prevent further distal outgrowth form only proximal limb elements. They have further shown that the more advanced the blastema is at the time of transplantation, the more distally complete is the resulting regenerate.…”

Looking proximally and distally: 100 years of limb regeneration and beyond

“…An important function of the MMPs encoded by the basal layer of the wound epidermis is thought to be the prevention of basement membrane reassembly beneath it, thus maintaining communication between the wound epidermis and subjacent blastema cells. Loss of such communication, either by removing the wound epidermis (Stocum and Dearlove, 1972;Mescher, 1976) or conditions under which a pad of connective tissue becomes prematurely interposed between wound epidermis and blastema cells (Stocum and Crawford, 1987), inhibits regeneration. These MMPs might also diffuse into the underlying tissues to participate in the degradation of other ECM components.…”

“…Well-established blastemas of larval A. maculatum denuded of wound epidermis and grafted into dorsal fin tunnels (where they would presumably become innervated by axons of the fin connective tissue) form skeletal elements that are subnormal in size, suggesting that cell proliferation is reduced or halted in the absence of the AEC (Stocum and Dearlove, 1972). Furthermore, DNA synthesis and mitosis of epidermis-free Notophthalmus viridescens limb blastemas cultured in the presence of dorsal root ganglia are reduced 3-4-fold (Globus et al, 1980;Smith and Globus, 1989).…”

“…Furthermore, DNA synthesis and mitosis of epidermis-free Notophthalmus viridescens limb blastemas cultured in the presence of dorsal root ganglia are reduced 3-4-fold (Globus et al, 1980;Smith and Globus, 1989). A major difference in the results of denervation and epidermal deprivation in vivo, however, is that denervated blastemas form a complete set of limb parts (Singer and Craven, 1948;Powell, 1969), whereas blastemas grafted to fin tunnels are distally truncated, suggesting that the AEC has a role in proximodistal patterning in addition to proliferation (Stocum and Dearlove, 1972).…”