Comparative expression profiling reveals an essential role for raldh2 in epimorphic regeneration.
Zebrafish have the remarkable ability to regenerate body parts including the heart and fins by a process referred to as epimorphic regeneration. Recent studies have illustrated that similar to adult zebrafish, early life stage larvae also possess the ability to regenerate the caudal fin. A comparative microarray analysis was used to determine the degree of conservation in gene expression among the regenerating adult caudal fin, adult heart, and larval fin. Results indicate that these tissues respond to amputation/injury with strikingly similar genomic responses. Comparative analysis revealed raldh2, a rate-limiting enzyme for the synthesis of retinoic acid, as one of the most highly induced genes across the three regeneration platforms. In situ localization and functional studies indicate that raldh2 expression is critical for the formation of wound epithelium and blastema. Patterning during regenerative outgrowth was considered to be the primary function of retinoic acid signaling; however, our results suggest that it is also required for early stages of tissue regeneration. Expression of raldh2 is regulated by Wnt and fibroblast growth factor/ERK signaling.
Department of Environmental and Molecular Toxicology, Environmental Health Sciences Center, Oregon State University, Corvallis, Oregon 97331, USA.
Lijoy K
LK
Mathew
Sumitra
S
Sengupta
Jill A
JA
Franzosa
Jessica
J
Perry
Jane
J
La Du
Eric A
EA
Andreasen
Robert L
RL
Tanguay
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D016000:Cluster Analysis; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000293:injuries / Q000378:metabolism; D005121:Extremities / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007814:Larva / Q000235:genetics / Q000254:growth & development; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D011758:Pyrroles / Q000494:pharmacology; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000235:genetics; D050697:Retinal Dehydrogenase / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D029961:Zebrafish Proteins / Q000235:genetics*
D002070:Butadienes; D009570:Nitriles; D011758:Pyrroles; C105686:SU 5402; C113580:U 0126; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C518907:Aldh1a2 protein, zebrafish; D050697:Retinal Dehydrogenase; D051496:Receptor, Fibroblast Growth Factor, Type 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3