Cooperative inputs of Bmp and Fgf signaling induce tail regeneration in urodele amphibians

Abstract

Urodele amphibians have remarkable organ regeneration ability. They can regenerate not only limbs but also a tail throughout their life. It has been demonstrated that the regeneration of some organs are governed by the presence of neural tissues. For instance, limb regeneration cannot be induced without nerves. Thus, identifying the nerve factors has been the primary focus in amphibian organ regeneration research. Recently, substitute molecules for nerves in limb regeneration, Bmp and Fgfs, were identified. Cooperative inputs of Bmp and Fgfs can induce limb regeneration in the absence of nerves. In the present study, we investigated whether similar or same regeneration mechanisms control another neural tissue governed organ regeneration, i.e., tail regeneration, in Ambystoma mexicanum. Neural tissues in a tail, which is the spinal cord, could transform wound healing responses into organ regeneration responses, similar to nerves in limb regeneration. Furthermore, the identified regeneration inducer Fgf2+Fgf8+Bmp7 showed similar inductive effects. However, further analysis revealed that the blastema cells induced by Fgf2+Fgf8+Bmp7 could participate in the regeneration of several tissues, but could not organize a patterned tail. Regeneration inductive ability of Fgf2+Fgf8+Bmp7 was confirmed in another urodele, Pleurodeles waltl. These results suggest that the organ regeneration ability in urodele amphibians is controlled by a common mechanism.

Stability and plasticity of positional memory during limb regeneration in Ambystoma mexicanum

“…In contrast, skin wounding plus nerve deviation resulted in a blastema. Cooperative inputs of Bmp and Fgf are shown to substitute for nerve roles in blastema induction in the ALM . The induced blastema can develop a complete limb.…”

“…6,[11][12][13][14][15] Recently, a brand-new experimental system called the accessory limb model (ALM) proposed the nerve molecules that can induce regeneration in multiple organs and species. 13,14,[16][17][18][19][20] The ALM is a better experimental design for the investigation of nerve functions in limb regeneration. 6,21 In the ALM, skin wounding (nerve-absent) resulted in simple skin wound healing.…”

BMP signaling regulates the skeletal and connective tissue differentiation during caudal fin regeneration in sailfin molly (Poecilia latipinna)

“…Cooperative inputs of FGF2, FGF8 and BMP7 lead to tail regeneration in urodele amphibians (Makanae et al . ). Zhang et al .…”

“…Along with BMP signaling, there are other contributors from FGF, Shh and COX-2 signaling pathways. Cooperative inputs of FGF2, FGF8 and BMP7 lead to tail regeneration in urodele amphibians (Makanae et al 2016). Zhang et al 2002 has proved COX-2 as critical for early events in fracture healing.…”

Inherent variations in the cellular events at the site of amputation orchestrate scar‐free wound healing in the tail and scarred wound healing in the limb of lizardHemidactylus flaviviridis

“…Further, wound healing, being an incredibly complex biological process with intricate molecular interaction among various cells at the site of injury, is modulated by the timed expression of a myriad of regulatory factors. Important among these factors are the members of epidermal growth factor, transforming growth factor beta (TGF‐β), fibroblast growth factor (FGF), interleukin, and tumor necrosis factor‐α families . In addition, vascular endothelial growth factor (VEGF), granulocyte macrophage colony stimulating factor, platelet‐derived growth factor, connective tissue growth factor are known to influence the process of wound healing .…”