期刊
DEVELOPMENT
卷 143, 期 19, 页码 3481-3490出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.131466
关键词
Axolotl; Epimorphic; Regeneration; TGF-beta signaling; Smad2; Smad3; Limb; Salamander; Urodeles; Ambystoma mexicanum
资金
- Canadian Institutes of Health Research [MOP: 111013]
- Reseau de Recherche en Sante Buccodentaire et Osseuse (RSBO)
Axolotls are unique among vertebrates in their ability to regenerate tissues, such as limbs, tail and skin. The axolotl limb is the most studied regenerating structure. The process is well characterized morphologically; however, it is not well understood at the molecular level. We demonstrate that TGF-beta 1 is highly upregulated during regeneration and that TGF-beta signaling is necessary for the regenerative process. We show that the basement membrane is not prematurely formed in animals treated with the TGF-beta antagonist SB-431542. More importantly, Smad2 and Smad3 are differentially regulated post-translationally during the preparation phase of limb regeneration. Using specific antagonists for Smad2 and Smad3 we demonstrate that Smad2 is responsible for the action of TGF-beta during regeneration, whereas Smad3 is not required. Smad2 target genes (Mmp2 and Mmp9) are inhibited in SB-431542-treated limbs, whereas non-canonical TGF-beta targets (e.g. Mmp13) are unaffected. This is the first study to show that Smad2 and Smad3 are differentially regulated during regeneration and places Smad2 at the heart of TGF-beta signaling supporting the regenerative process.
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