Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish.
Appendage regeneration is defined by rapid changes in gene expression that achieve dramatic developmental effects, suggesting involvement of microRNAs (miRNAs). Here, we find dynamic regulation of many miRNAs during zebrafish fin regeneration. In particular, miR-133 levels are high in uninjured fins but low during regeneration. When regeneration was blocked by Fibroblast growth factor (Fgf) receptor inhibition, high miR-133 levels were quickly restored. Experimentally increasing amounts of miR-133 attenuated fin regeneration. Conversely, miR-133 antagonism during Fgf receptor inhibition accelerated regeneration through increased proliferation within the regeneration blastema. The Mps1 kinase, an established positive regulator of blastemal proliferation, is an in vivo target of miR-133. Our findings identify miRNA depletion as a new regulatory mechanism for complex tissue regeneration.
Yin
Viravuth P
VP
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Thomson
J Michael
JM
Thummel
Ryan
R
Hyde
David R
DR
Hammond
Scott M
SM
Poss
Kenneth D
KD
D000818:Animals; D015152:Blotting, Northern; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005121:Extremities / Q000502:physiology*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
D035683:MicroRNAs; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D029961:Zebrafish Proteins; D005346:Fibroblast Growth Factors; C490545:ttk protein, zebrafish; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases