Document Detail

Activation of germline-specific genes is required for limb regeneration in the Mexican axolotl.
MedLine Citation:
PMID:  22841627     Owner:  NLM     Status:  MEDLINE    
The capacity for tissue and organ regeneration in humans is dwarfed by comparison to that of salamanders. Emerging evidence suggests that mechanisms learned from the early phase of salamander limb regeneration-wound healing, cellular dedifferentiation and blastemal formation-will reveal therapeutic approaches for tissue regeneration in humans. Here we describe a unique transcriptional fingerprint of regenerating limb tissue in the Mexican axolotl (Ambystoma mexicanum) that is indicative of cellular reprogramming of differentiated cells to a germline-like state. Two genes that are required for self-renewal of germ cells in mice and flies, Piwi-like 1 (PL1) and Piwi-like 2 (PL2), are expressed in limb blastemal cells, the basal layer keratinocytes and the thickened apical epithelial cap in the wound epidermis in the regenerating limb. Depletion of PL1 and PL2 by morpholino oligonucleotides decreased cell proliferation and increased cell death in the blastema leading to a significant retardation of regeneration. Examination of key molecules that are known to be required for limb development or regeneration further revealed that FGF8 is transcriptionally downregulated in the presence of the morpholino oligos, indicating PL1 and PL2 might participate in FGF signaling during limb regeneration. Given the requirement for FGF signaling in limb development and regeneration, the results suggest that PL1 and PL2 function to establish a unique germline-like state that is associated with successful regeneration.
Wei Zhu; Gerald M Pao; Akira Satoh; Gillian Cummings; James R Monaghan; Timothy T Harkins; Susan V Bryant; S Randal Voss; David M Gardiner; Tony Hunter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-27
Journal Detail:
Title:  Developmental biology     Volume:  370     ISSN:  1095-564X     ISO Abbreviation:  Dev. Biol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-03     Completed Date:  2012-11-08     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  42-51     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
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MeSH Terms
Ambystoma mexicanum / genetics,  physiology*
Amino Acid Sequence
Argonaute Proteins / genetics,  metabolism
Cell Differentiation / physiology
Cell Proliferation
Extremities / physiology*
Gene Expression Regulation, Developmental / genetics,  physiology*
Gene Knockdown Techniques
Germ Cells / metabolism*
Molecular Sequence Data
Morpholinos / genetics
Regeneration / genetics,  physiology*
Wound Healing / physiology
Grant Support
Reg. No./Substance:
0/Argonaute Proteins; 0/Morpholinos

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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