PMID- 26092703
OWN - NLM
STAT- MEDLINE
DCOM- 20160908
LR  - 20190329
IS  - 1532-0456 (Print)
IS  - 1532-0456 (Linking)
VI  - 178
DP  - 2015 Dec
TI  - Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and 
      microarray analysis to identify signaling pathways associated with tissue 
      regeneration.
PG  - 128-135
LID - S1532-0456(15)00069-1 [pii]
LID - 10.1016/j.cbpc.2015.06.004 [doi]
AB  - Amphibian vertebrates are important models in regenerative biology because they 
      present exceptional regenerative capabilities throughout life. However, it takes 
      considerable effort to rear amphibians to juvenile and adult stages for 
      regeneration studies, and the relatively large sizes that frogs and salamanders 
      achieve during development make them difficult to use in chemical screens. Here, 
      we introduce a new tail regeneration model using late stage Mexican axolotl 
      embryos. We show that axolotl embryos completely regenerate amputated tails in 
      7days before they exhaust their yolk supply and begin to feed. Further, we show 
      that axolotl embryos can be efficiently reared in microtiter plates to achieve 
      moderate throughput screening of soluble chemicals to investigate toxicity and 
      identify molecules that alter regenerative outcome. As proof of principle, we 
      identified integration 1 / wingless (Wnt), transforming growth factor beta 
      (Tgf-beta), and fibroblast growth factor (Fgf) pathway antagonists that completely 
      block tail regeneration and additional chemicals that significantly affected tail 
      outgrowth. Furthermore, we used microarray analysis to show that inhibition of 
      Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, 
      Tgf-beta, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic 
      gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), 
      myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid 
      (RA) pathways. Punctuated changes in the expression of genes known to regulate 
      vertebrate development were observed; this suggests the tail regeneration 
      transcriptional program is hierarchically structured and temporally ordered. Our 
      study establishes the axolotl as a chemical screening model to investigate 
      signaling pathways associated with tissue regeneration.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Ponomareva, Larissa V
AU  - Ponomareva LV
AD  - College of Pharmacy and Center for Pharmaceutical Research and Innovation, 
      University of Kentucky, Lexington, KY 40536, USA.
FAU - Athippozhy, Antony
AU  - Athippozhy A
AD  - Department of Biology, Spinal Cord and Brain Injury Research Center, and 
      Ambystoma Genetic Stock Center, University of Kentucky, Lexington, KY 40506, USA.
FAU - Thorson, Jon S
AU  - Thorson JS
AD  - College of Pharmacy and Center for Pharmaceutical Research and Innovation, 
      University of Kentucky, Lexington, KY 40536, USA.
FAU - Voss, S Randal
AU  - Voss SR
AD  - Department of Biology, Spinal Cord and Brain Injury Research Center, and 
      Ambystoma Genetic Stock Center, University of Kentucky, Lexington, KY 40506, USA. 
      Electronic address: srvoss@uky.edu.
LA  - eng
GR  - R24 OD010435/OD/NIH HHS/United States
GR  - UL1 TR000117/TR/NCATS NIH HHS/United States
GR  - R24OD010435/OD/NIH HHS/United States
GR  - UL1TR000117/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150616
PL  - United States
TA  - Comp Biochem Physiol C Toxicol Pharmacol
JT  - Comparative biochemistry and physiology. Toxicology & pharmacology : CBP
JID - 100959500
SB  - IM
MH  - Ambystoma mexicanum/*genetics
MH  - Animals
MH  - Microarray Analysis/methods
MH  - Regeneration/*genetics
MH  - Signal Transduction/*genetics
MH  - Transcription, Genetic/genetics
MH  - Vertebrates/genetics
PMC - PMC4662883
MID - NIHMS713388
OTO - NOTNLM
OT  - Axolotl
OT  - C59
OT  - Chemical screening
OT  - Regeneration
OT  - Wnt
EDAT- 2015/06/21 06:00
MHDA- 2016/09/09 06:00
PMCR- 2016/12/01
CRDT- 2015/06/21 06:00
PHST- 2015/03/19 00:00 [received]
PHST- 2015/05/27 00:00 [revised]
PHST- 2015/06/09 00:00 [accepted]
PHST- 2015/06/21 06:00 [entrez]
PHST- 2015/06/21 06:00 [pubmed]
PHST- 2016/09/09 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - S1532-0456(15)00069-1 [pii]
AID - 10.1016/j.cbpc.2015.06.004 [doi]
PST - ppublish
SO  - Comp Biochem Physiol C Toxicol Pharmacol. 2015 Dec;178:128-135. doi: 
      10.1016/j.cbpc.2015.06.004. Epub 2015 Jun 16.