Inhibition of BMP signaling during zebrafish fin regeneration disrupts fin growth and scleroblasts differentiation and function.
The zebrafish caudal fin provides a simple model to study molecular mechanisms of dermal bone regeneration. We previously showed that misexpression of Bone morphogenetic protein 2b (Bmp2b) induces ectopic bone formation within the regenerate. Here we show that in addition to bmp2b and bmp4 another family member, bmp6, is involved in fin regeneration. We further investigated the function of BMP signaling by ectopically expressing the BMP signaling inhibitor Chordin which caused: (1) inhibition of regenerate outgrowth due to a decrease of blastema cell proliferation and downregulation of msxb and msxC expression and (2) reduced bone matrix deposition resulting from a defect in the maturation and function of bone-secreting cells. We then identified targets of BMP signaling involved in regeneration of the bone of the fin rays. runx2a/b and their target col10a1 were downregulated following BMP signaling inhibition. Unexpectedly, the sox9a/b transcription factors responsible for chondrocyte differentiation were detected in the non-cartilaginous fin rays, sox9a and sox9b were not only differentially expressed but also differentially regulated since sox9a, but not sox9b, was downregulated in the absence of BMP signaling. Finally, this analysis revealed the surprising finding of the expression, in the fin regenerate, of several factors which are normally the signatures of chondrogenic elements during endochondral bone formation although fin rays form through dermal ossification, without a cartilage intermediate.
Smith
A
A
Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, ON, Canada K1Y4E9.
Avaron
F
F
Guay
D
D
Padhi
B K
BK
Akimenko
M A
MA
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D015536:Down-Regulation; D006023:Glycoproteins / Q000096:biosynthesis; D024002:HMGB Proteins / Q000096:biosynthesis; D018398:Homeodomain Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D010006:Osteoblasts / Q000166:cytology*; D010012:Osteogenesis; D012038:Regeneration; D055758:SOX9 Transcription Factor; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D015027:Zebrafish / Q000033:anatomy & histology* / Q000378:metabolism / Q000502:physiology*; D029961:Zebrafish Proteins / Q000096:biosynthesis / Q000378:metabolism
D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D019485:Bone Morphogenetic Proteins; D006023:Glycoproteins; D024002:HMGB Proteins; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; C502545:Runx2a protein, zebrafish; C502546:Runx2b protein, zebrafish; D055758:SOX9 Transcription Factor; C504918:Sox9a protein, zebrafish; C504919:Sox9b protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; C405936:bmp2b protein, zebrafish; C525813:bmp4 protein, zebrafish; C460082:msx1b protein, zebrafish; C513488:msx3 protein, zebrafish; C054234:chordin